Viruses Flashcards
Describe the characteristics of the beta-herpes viruses
- Restricted host range
- More likely to affect immunocompromised patients
- Grow more slowly in culture
- Infected cells have cytomegaly
How many people infected with poliovirus will become severely ill? How many will be paralyzed?
Poliomyelitis causes…
- Transient viremia in 95% of infected patients
- Short-lived, relatively mild illness
- Sustained viremia in 5% of infected patients
- Fever, headache, sore throat
- Poliomyelitis in <1% of infected patients
- Asymmetric, assencding paralysis to some degree
- Range in severity
- Frank paralysis in <0.1% of infected patients
What is the pathogenesis of Parvovirus B19?
- The virus targets erythrocyte progenitors
- This prevents the synthesis of new red blood cells
- The virus is mild or benign in healthy children
- The 5th diesease (Erythema infectiosum)
- “Slapped cheek appearance” onset after low grade fever breaks
- Quick recovery without complications
- However, it has more severe effects in anyone with a shorter red blood cell lifespan
- Aplastic crisis in persons with hemolytic anemia
- Chronic aplastic anemia in AIDS patients
- Hydrops fetalis (heart failure) infetuses
What do ss(–)RNA viruses use to convert ss(–)RNA to mRNA and genomic ss(+)RNA?
Viral RNA-dependent RNA polymerase
What characteristics of pathogenicity make rotavirus particularly contagious?
- <100 particles are needed to cause infection
- Lots of viruses are shed in the stool
- 2 days before diarrhea begins - 10 days after it ends
- Spread via contaminated hands and objects
- Survive for hours on hands, days on objects
What does Oseltamivir treat?
What is the mechanism of action?
Oseltamivir = Tamiflu; influenza antiviral
Cleaves terminal sialic acid from sialic acid-containing glycoproteins. This inhibits neuraminidase and prevents the release of the virus from the host cell nucleus(cannot spread to other cells)
Which test can distinguish acute EBV from past EBV infection?
anti-EBNA IgG
- Will be negative during primary EBV infection
- Will be positive when primary infection has subsided
- And the host has established IgG antibodies
Which virus represents the leading causes of congenital mental retardation and hearing loss?
HCMV
List the viruses (discussed in FDN3) that can be transmitted by mosquito.
Identify the type of mosquito
Aedes
- Chikungunya virus
- Dengue fever
- Zika Virus
Culex
- West Nile Virus
Which virus is the exception to the rule “All DNA viruses are replicated in the nucleus?”
Poxvirus
What is hydrops fetalis?
Who does it affect?
- Hydrops fetalis is heat faliure in a fetus
- May be caused by infection by parvovirus B19
- It leads to abortion
- A pregnant woman infected with parvovirus B19 can pass the infection on to her fetus
- <10% of fetuses with an infected mother get hydrops fetalis
- Most dangerous in the first 2 trimesters
Describe the clinical presentation of HHV6 in a young child
HHV6 = 6th disease = Roseola
- Typicaly occurs at 6 mo - 2 yo
- 3-4 days of high fever (>104 F)
- May cause febrile seizures
- As fever subsides, body rash that spares the face forms
- Lacy red rash
- The illness is self limiting
- Can be treated with ganciclovir or valganciclovir
How is Hepatitis A contacted?
From where?
Fecal-oral route
- Endemic to resource-limited countries with poor water sanitation
- In resouce-abundant countries, people can contract hepatitis A from shellfish that was caught in contaminated water
Describe Astrovirus
Type of virus:
Capsid:
Envelope:
Nucleic acid:
Astrovirus
Type of virus: Astroviridae (eneterovirus)
Capsid: Icosahedral
Envelope: Non-enveloped
Nucleic acid: (+)ssRNA
Describe the capsid and envelope of:
Poxvirus
Complex capsid (brick-shaped)
Enveloped
What are the important properties/differentiations of the viral genome?
- RNA or DNA
- Single-stranded or double stranded
- Linear or circular
- Segmented or not
- If single-stranded
- Positive sense, negative sense, or ambisense
- Size (from 3,500 nt to 280 kbp)
What is the site of latency of HCMV?
Mononuclear cells, PMNs, and/or vascular endothelial cells
What is the clinical presentation of measles?
- Fever
- Cough, coryza, conjunctivitis (The 3 C’s)
- Koplick’s spots
- Clustered white lesions on buccal mucosa
- Appear 2-3 days before rash
- Rash
- Complications are relatively common
Which virus presents with parotitis and/or orchititis?
Mumps
What is the most common primary infection of VZV?
Describe the symptoms
Chickenpox
- Systemic disease
- Fever, headache, body rash
- “Dew drop on rose petal”
- Adults may have complications
- Pneumonia
- Encephalitis
Where do alpha herpes viruses remain latent?
HSV-1, HSV-2, and VZV all reamain latent in the sensory/dorsal root ganglia
(HSV may also be in autonomic ganglia)
Describe the beginning of a new rotavirus infection in a new host cell
- The outer layer of the TLP is removed during uncoating, after entry into the host cell
- Trsncription of the dsRNA -> (+)ssRNA occurs in the DLP
- This “hides” the dsRNA from host pattern recognition receptors (dsRNA is a PAMP)
- The (+)ssRNA is capped by VP3, a viral capping enzyme
- The capped (+)ssRNA is exported from the DLP
- This capped (+)ssRNA looks a lot like a host mRNA
- The viral (+)ssRNA is translated using host machinery
Describe the clinical presentation of astroviridae
Diarrhea
Nausea
Vomiting (but less than norovirus and rotavirus)
Typically not severe (no dehydration)
Primarily affects children
What is required in the penetration stage of the viral productive replicative cycle?
What occurs?
Energy-dependent
- Enveloped viruses
- Fusion of viron envelope with plasma membrane (some)
- Endocytosis
- Fusion with endosome membrane
- Non-enveloped viruses
- Translocation of virus/viral genome across plasma membrane (some)
- Endocytosis
- Translocation across endosome
What is the eclipse/replication stage of the viral productive replicative cycle?
Period during which viral nucleic acids and proteins are being synthesized, but infectious virus cannot be detected in the infected cell
What are the relevant viral proteins of rotavirus?
- VP2
- Innermost icosahedral capsid
- VP3
- Caps newly synthesized viral (+)ssRNA transcripts
- VP4
- Recptor binding protein; enhances infection of villi in the small intestine
- Used in serotype definition
- VP6
- 2nd icosahedral shell (outside of DLP, middle of TLP)
- VP7
- Used in serotype definition
- NSP4
- Enterotoxin that causes diarrhea
How is EBV transmitted?
Oral secretions
EBV = mono = the “kissing disease”
What are the most common causes of aseptic meningitis?
Aseptic = viral (no bacteria in CSF)
- Enteroviruses
- Coxsackie A
- Coxsackie B
- EV-71
When is Ebola infectious?
From the first sign of illness through 21-41 days after symptoms have resolved
(The virus can persist in semen and conjunctiva for 6-12 months, although it is not known if this still poses a threat of infection)
When does assembly occur in the viral productive replicative cycle?
Where does it occur?
When progeny viral genomes and viral structural proteins have accumulated to sufficient levels, assembly of the viral genome can occur
Occurs in cell compartment where genome replication occurred (Nucleus for most DNA viruses, cytoplasm for most RNA viruses)
What is episomal latency?
Extrachromosomal viral genes floating in the cytoplasm or nucleus
Herpesviruses (HSV, EBV, VZV, CMV)
Why are some viruses able to be transmitted my mosquitos, while others are not?
To be transmitted by mosquitos or other insects, a virus must be able to infect and replicate inside of the mosquito (usually in the midgut)
Not all viruses can do this
Describe Hepatitis E
Type of virus:
Capsid:
Envelope:
Nucleic acid:
Hepatitis A
Type of virus: Picornavirus (enterovirus)
Capsid: Icosahedral
Envelope: Non-enveloped
Nucleic acid: ss(+)RNA
What is significant about the emergence of human metapneumovirus?
The first reported case was in 2001, and today it is the second most common cause of lower respiratory tract infection in young children
This implies that new virues can carry a significant burden of disease
Give 2 examples of viruses utilizing existing cell surface molecules in the attachment stage of the viral productive replicative cycle
- Influenze - sialic acid oligosaccharides
- HIV - CD4, CXCR4, CCR5
Describe Hepatitis A
Type of virus:
Capsid:
Envelope:
Nucleic acid:
Hepatitis A
Type of virus: Picornavirus (enterovirus)
Capsid: Icosahedral
Envelope: Non-enveloped
Nucleic acid: ss(+)RNA
Describe the clinical presentation of chikungunya virus
- Fever
- Arthralgias
- 60% of infected have persistent joint pain for years
What cell surface receptor does poliovirus bind to?
CD155
Which herpes viruses can be oncogenic?
EBV
HHV8 (Kaposi Sarcoma HV)
How is MERS-CoV transmitted?
Bats -> Camels -> Humans
Human - Human
Humans are infected by respiratory droplets
What are the four general types of viral infection in a susceptible cell?
- Non-permissive for infection
- Productively infected
- Abortively infected
- Latently infected
Describe antigenic drift
- Minor changes due to single mutations
- Occurs in influenza A and influenza B
- Causes epidemics
- Associated with seasonal influenza
Describe the clinical manifestation of parainfluenza virus (PIV)
- Lower or upper respiratory tract infection
Describe the common clinical manifestations of HSV-1
Primary infection
- Gingivostomatis
- Pharyngotonsilitis
- Complications to post-op course
Reactivation
-
Cold sores outside of the mouth
- Sores can also appear in other places
- Ex: finger/fingernail (herpetic whitlow)
- Bell’s palsy
- Encephalitis
- Keratitis
List the relevant enteroviruses that we have learned about
PREACH-EEN
- Poliovirus
- Rotavirus
- Echo Virus
- Astrovirus
- Coxsackie A & B
- Hepatitis A
- EV-71
- EV-D68
- Norovirus
(You can get enteroviruses in church if somebody is contagious, because you’re all sitting close together)
Which clinical sign is diagnostic of measles?
Koplick’s spots
- Appear 2-3 days before rash
- Clustered white lesions on buccal mucosa
- Opposite from upper 1st and 2nd molars
What is the fate of the host cell after viral infection?
Virus replication usually results in cell death through direct cytotoxic effects of viral products or innate and adaptive host response
How is EBV diagnosed?
- PCR
-
Heterophile assay aka mononuclear spot test aka “monospot”
- Human antibodies will agglutinate (clump) sheep or horse blood
- 70-92% sensitive
- 96-100% specific
- Human antibodies will agglutinate (clump) sheep or horse blood
- Anti-EBNA IgG
- Negative during active primary infection (IgM will be high at this time)
- Positive when the primary infection has subsided
Which populations should be most cautious when traveling to areas in which Zika virus is endemic?
Pregnant women
How is HSV-2 transmitted?
Close person to person contact
- Exposure to broken skin or mucosa
- Usually genital, can be oral
A patient presents with a severe headache right side of their head and a fever
Physical exam reveals a tender sore next to and underneath the fingernail of the patient’s right index finger.
The patient reports that they have had similar sores on that finger in the past, but doesn’t think much of it becase it goes away on its own
Is the fingernail significant?
What might be causing these symptoms?
Should the patient be treated?
The fingernail is significant!
This sounds like a case of HSV-1; If this is the case, the fingernail could be herpetic whitlow (aka paronychia), and the headache might indicate encephalitis, a rare but serious complication of HSV-1
The diagnosis can be confirmed with a Tzank prep or PCR
The patient should be treated with acyclovir or valacylovir to prevent progression of encephalitis
Which virus has this characteristic “scalloped” border?
Norovirus, of the calicivirus family
Which influenza virus (A or B) has greater diversity?
Why?
Influenza A
- Influenza A has many subtypes defined by hemagglutinin (HA) and Neuraminidase (NA)
- There are 18 HAs and 11 NAs
- The viral RNA-Dependent RNA Polymerase lacks proofreading
- Subject to mutation and therefore evolution
- 8 gene segments encode 10 viral proteins
- Segments are subject to reassortment
Describe the clinical presentation of Respiratory Syncytial Virus
- Lower respiratory tract infection
- Bronchiolitis (2-3% of cases)
- Hospitalization
- Pneumonia
- Tracheobronchitis
- Croup
- Bronchiolitis (2-3% of cases)
- Repeat infection is common
- Becomes less severe over time
- Recurrent wheezing often follows severe infection
Compare the sizes of DNA and RNA viral genomes
RNA viruses are usually smaller
DNA viruses are usually larger
Which subsets of CD4+ T-cells can be infected by HIV infection?
What are the effects of infection of each subset?
Effector CD4+ helper T-cells and Memory CD4+ helper T-cells
- Infection of effector CD4+ helper T-cells
- Proviral DNA is transcribed
- Viral proteins are produced
- The virus spreads
- These cells are eliminated by the immune system; eventually they will be depleted (without treatment)
- Infection of memory CD4+ helper T-cells
- Proviral DNA is not transcribed
- Viral proteins and antigens are not produced
- The infection is invisible to the immune system
- This is why HIV cannot be cured; the virus will persist here silently, spreading to effector cells if necessary
What are the three major categories of picornaviruses?
Hepatitis A
Enteroviruses
Rhinoviruses
What is a latent viral infection?
- Viral genome is established inside cell
- Some genes are expressed, but virus does not replicate
- Cell remains viable, but some functions may be altered
What is the clinical presentation of HSV-1 encephalitis?
- Focal headache on one side of the frontal temporal lobe
- Confusion/personality changes
- Fever
- Seizures are possible
What do the most successful antiviral drugs target?
Enzymes/proteins encoded by the virus
How can VZV infection be treated?
Both chickenpox and shingles can be treated with acyclovir or valacyclovir
Can also use famiciclovir for shingles
In a productive viral infection, why is production of a virus usually incompatible with cell survival?
- Cytotoxic effects of viral products
- Including those that give the virus a competitive advantage for cellular biosynthetic machinery
- Induction of innate responses that can result in death of infected cells
- Sometimes cells continually release viruses in addition to being lysed (Hepatitis B infections)
Most enteroviruses are…
Type of virus:
Capsid:
Envelope:
Nucleic acid:
Except…
Most enteroviruses are…
Type of virus: Picornaviruses
(norovirus = caliciviridae
rotavirus = reoviridae
astrovirus = astroviridae)
Capsid: Icosahedral
Envelope: Non-enveloped
Nucleic acid: ss(+)RNA
(excpet rotavirus = dsRNA)
Give 2 examples of viral proteins mediating attachment during the attachment stage of the viral productive replicative cycle
- Influenze - hemagglutinin
- HIV - gp120
What consequence to the host cell is productive viral infection associated with?
Cell death
How is parainfluenza virus diagnoses?
PCR
How is VZV transmitted?
Cutaneous skin legions produce highly infectious virus that are aerosolized
Spread through air and ventilation systems as respiratory droplets
Inhalation by new host
What occurs in the replicative cycle of ss(+)RNA viruses such as norovirus?
- ss(+)RNA = mRNA
- ss(+)RNA is ranslation-competent: the ss(+)RNA is translated into a nonfunctional polyprotein by host ribosomes immediately upon entry into cytoplasm
- The polyprotein cleaved into smaller functional proteins by viral protease
What is the treatment for mumps?
Supportive care
(No antiviral is avilable)
Describe the clinical presentation of Hepatitis A
- Sudden nausea and vomiting
- Jaundice (in adults, likely to be absent in children)
- Self-limiting infection, no chronic effects
What is the reservoir for Ebolavirus?
Bats, Primates
Describe the capsid and envelope of:
Hepadnavirus
Helical (spheres and filaments)
Enveloped
What is the prevalence of HSV-1?
90% of adults are infected
In the viral productive replicative cycle, when are most non-enveloped viruses released from infected cells?
When the cell lyses
How is Zika virus treated?
Supportive
Describe the clinical presentation of HHV8 (KSHV)
Symptoms only in immunocompromised patients
- Erythematous, violet lesions on nose an exremeties
- Mononucleosis
(immune competent patients will be asymptomatic or subclinical)
Describe the clinical manifestation of rhinovirus
- Rapid onset of infection
- Upper respiratory tract infection
- Lower respiratory tract infection is uncommon because rhinovirus prefers cooler temperatures
- Low grade fever possible
How is rhinovirus transmitted?
Aerosols of respiratory droplets or fomites
(Person to person contact and contaminated objects)
Incubation period is 1-4 days
Note: This is the only picornavirus that is not transmitted by the fecal-oral route (it is acid labile)
What are the most common complications of measles?
Complications are mroe severe in adults
- Diarrhea
- Pneumonia
- Encephalitis
- SSPE = Subactue sclerosing parencephalitis; a chronic, degenerative, neurological disease
- Corneal ulceration
- May lead to scarring and blindness
In the replication cycle of a DNA virus, what do late mRNAs typically encode?
Structural proteins
How are non-enveloped viruses typically transmitted?
Fecal-oral route
Viruses that can be transmitted through contaminated water are typically non-enveloped
Describe the clinical presentation of EV-D68
Mild to severe respiratory infection
How is influenza diagnosed?
Rapid antigen test
or
PCR
Desribe the “clinical latency” stage of HIV
- No outward symptoms
- Individual may get sick more often
- Community acquired pneumonia
- Generaly lymphadenopathy
- Herpes zoster
- Cervical dysplasia
- 10^8-10^9 virions are produced each day in effector CD4+ T-cells
- Spread to infect other effector CD4+ T-cell
- The immune system is killing the infected cells
- The virus may be mutating
- Lymphopoetic system is replacing the lost CD4+ T-cells
- Gradual decrease in numbers may be happening
- Will progress to AIDS if CD4+ progenitor cells in bone marrow are lost
What makes a cell susceptible to viral infection?
The cell is suceptile if the virus can enter and either…
- Express genes
- Establish its genome inside cell
Describe Measles
- Type of virus:
- Capsid:
- Envelope:
- Nucleic acid:
Measles
- Type of virus: Paramyxovirus
- Capsid: Helical
- Envelope: Enveloped
- Nucleic acid: ss(-)RNA
What is the reservoir of dengue fever?
Humans, mosquitos
What is th treatment for West Nile Virus?
Supportive
Where do most DNA viruses release their genome during the disassembly stage of the viral productive replicative cycle?
Nucleus
(May require microtubules or other molecular motors to translocate nucleocapsid from cell periphery to nuclear core)
Which virus is known for its “wheel-like appearance” en electron micrographs?
Rotavirus
(wheels rotate)
Describe Adenovirus
- Capsid:
- Envelope:
- Nucleic acid:
Adenovirus
- Capsid: Icosahedral
- Envelope: Non-enveloped
- Nucleic acid: dsDNA
Why is norovirus more likley to affect adults than rotavirus?
Norovirus mutates quickly and does not establish a good protective immunity in the host.
- There is no cross-protection between serogroups
- Re-infections are possible
Rotavirus establishes immunity in the host. Most poeple get one bout of rotavirus as a child, and then are protected for the rest of their life
- There is cross-protection between serogroups
- Re-infection is very rare
Virus X can survive for up to 2 days on plastic or metal surfaces;
Based on this description, do you think virus X is enveloped or non-enveloped?
Non-enveloped
Non-enveloped viruses are more resistant to environmental dessication (like what would occur after 2 days on a plastic surface)
How is flu treated?
Antiviral therapy
- Most effective if started within 24 hours of onset
- Very important for elderly or immunocompromised patients
- Leading treatment: Oseltamivir (Tamiflu)
- Neuraminidase inhibitor; new virions cannot be released from host nucleus
- Works against influenza A and B
- Alternatives: Zanamivir, Baloxavir
Which viruses are the exceptions to the rule “All DNA viruses are linear”
Human Papillomavirus (HPV)
Polyomavirus
Hepatitis B Virus (HBV)
What do all enteric viruses have in common?
Transmission via fecal-oral route
Most are ss(+)RNA (except Rotavirus)
What vaccines are available to prevent polio?
- Enhanced, inactivated polio vaccine (IPV) by Salk
- Given in the USA
- Will not mutate to a virulent form
- Oral polio vaccine (OPV) by Sabin
- Live, attenuated virus
- Used in resource-limited countries
- Small chance of spontaneous mutation to a virulent form
- CVDPVL circulating, vaccine-derived poliovirus
What are the cellular consequences of viral infection?
- Numerous cellular processes are compromised
- Nucleic acid and protein synthesis
- Maintenance of cytoskeletal architecture
- Preservation of membrane integrity
- Induction of apoptosis
- But many RNA viruses encode proteins that block apoptosis
Which virus is the exception to the rule “All DNA viruses are icosahedral?”
Poxvirus
Describe the clinical presentation of EV-71
Hand, foot, and mouth disease
Meningoencephalitis
Describe the capsid and envelope of:
Picornavirus
Icosahedral capsid
Non-enveloped
(also small)
Describe the clinical presentaiton of hepatitis E
No chronic infection
Fever, abdominal pain, nausea, vomiting
More severe infection in pregnant women
Describe Poliovirus
Type of virus:
Capsid:
Envelope:
Nucleic acid:
Norovirus
Type of virus: Picornavirus
Capsid: Icosahedral
Envelope: Non-enveloped
Nucleic acid: (+)ssRNA
Describe the characteristics of gamma herpes viruses
- Lymphotrophic
- Can be oncogenic
After entry into a host cell, how does HIV destruction by the host cell?
Rev
How is Dengue fever transmitted?
Aedes mosquito
Vertical transmission from mother to fetus is possible
How is HSV-1 transmitted?
Close person to person contact
- Exposure to broken skin or mucosa
- Usually oral, may be genital
What are the 4 viral proteins of Rhinovirus?
What are their functions?
VP1, VP2, VP3 = capsid
VP4 = intervace between capsid and the RNA genome
What occurs in the replicative cycle of ss(–)RNA viruses such as influenza virus?
- ss(–)RNA is not equivalent to mRNA
- Viral RNA-dependent RNA polymerase converts ss(–)RNA to mRNA and genomic ss(+)RNA
- The ss(+)RNA is transcribed by host cell ribosomes in the cytoplasm into a nonfunctional polyprotein
- The polyprotein is cleaved into smaller proteins by viral protease
What is it called when enveloped viruses enter the host cell by fusion of their viral envelope with the cell membrane in the attachment stage of the viral productive replicative cycle?
Receptor-mediated endocytosis
Describe HIV
Family:
Envelope:
Nucleid Acid:
HIV
Family: Retrovirus
Envelope: Enveloped
Nucleid Acid: ss(+)RNA
Which enterovirus can cause an infected individual to require a heart transplant?
Coxsackie B
It can cause severe heart damage
What is the effect of a deletion that eliminates the CCR5 receptor?
The person posessing this mutation is immune to HIV infection
Describe the emergence of Zika virus
1947: infected rhesus monkey (Uganda)
1947-2007: Not common in humans
2015: Emerged in Brazil, swept through the Americas
List the relevant flaviviruses
Dengue fever
West Nile Virus
Zika Virus
Why are M2 inhibitors an inferior treatment to Oseltamivir in treatment of influenza?
M2 inhibitors only treat influenza A
There is widespread resistance ot amantadine and rimantidine, leading M2 inhibitor drugs
Which individuals are at the highest risk for complications from HSV-2 infection?
Neonates
(So you would also be concerned if an infected mother contracted a new HSV-2 infection in the first or third trimester)
- First trimester b/c HSV-2 is a TORCH agent that can cause birth defects
- Third b/c mother can pass virus to neonate during delivery, resulting in a severe infection with lifelong defects
Describe the mechanism of action of rhinovirus
- Virus adheres to surface receptors within 15 minutes of entering the respiratory tract
- Binds to ICAM 1 on epithelial cells
- ICAM 1 mediates cellular entry
- Infected cells release chemokines and cytokines
- Activates inflammatory mediators
- Causes upper respiratory cell lysis
- Binds to ICAM 1 on epithelial cells
Describe the possible clinical presentations of coxsackie A
Hand foot and mouth disease
Aseptic meningitis
Which arm of the immune system is involved in fighting parainfluenza virus?
Humoral immunity (B-cells and plasma cells)
How is HHV8 treated?
Antivirals are not effective
Treat with…
- Antiretroviral followed by chemotherapy
How can VZV be prevented?
Primary infection: Chickenpox (Varicella zoster virus)
- Prevented with live, attenuated vaccine
Reactivation infection: Shingles (Herpes zoster virus)
- Adults who had chicken pox as children can reieve a recombinant VZV glycoprotein E antigen with adjuvant to prevent reactivation
- Recommended for adults >50 years old
- A live, attenuated virus was previously used, but it was not as effective (50%), and it could not be given to immunocompromised patients
What is the treatement for Adenovirus?
- Cidofovir or Brincidofovir
- Limited efficacy
No vaccine is available
Which agents is acyclovir/gancyclovir active against?
Rank them
HSV >> VZV > EBV > CMV > HHV-6
(Use ganciclovir/valganciclovir for CMV adn HHV-6)
Describe Rhinovirus (HRV)
- Type of virus:
- Capsid:
- Envelope:
- Nucleic acid:
Rhinovirus
- Type of virus: Picornavirus
- Capsid: Icosahedral
- Envelope: Non-enveloped
- Nucleic acid: ss(+)RNA
Describe the presentation of a congenital HCMV infection
Can be acquired intra-natally or perinatally
- Intranatal = more severe
- Acquired from non-immune mother
- Jaundice
- Hepatosplenomegaly
- Petechial rash
- Deafness
- Neurological effects
- Microcephaly
- Motor disability
- Chorioretinitis
- Cerebral calcifications
- Perinatal = more subtle effects on hearing and intelligence
How does Rhinovirus get into human cells?
- Transmission = respiratory droplets
- Rhinovirus is the only picornavirus that is not transmitted fecal-orally
- Enters cells by binding to ICAM1 on epithelial cells
- Upper respiratory only (prefers cooler temp)
- Infected cells release chemokines and cytokines
- Leads to upper respiratory infections
How is Ebola transmitted?
Direct contact with infected bodily fluids
Suppose you have a pregnant patient who contracted HSV-2 about 10 years ago. She is in labor, and you notice a genital lesion as she is getting ready to deliver
Are you worried about transmission of HSV-2 to the neonate? Why or why not?
No need to worry!
The mother has likely passed IgG antibodies to the fetus through the placenta during pregnancy.
Therefore, the newborn already has antibodies to HSV-2, and is not at risk for an infection
What are the possible complicaitons of herpes zoster virus?
- Zoster opthalmicus
- Vision loss due to involvement at the first division of the trigeminal nerve
- Paresis
- Myelopathy
- Vasculopathy
- Post-herpetic neuralgia (PHN)
Describe Rotavirus
Type of virus:
Capsid:
Envelope:
Nucleic acid:
Rotavirus
Type of virus: Reovirus
Capsid: Icosahedral, triple layered particle
Envelope: Non-enveloped
Nucleic acid: dsRNA
How is Ebola treated?
Monoclonal antibody
(New therapy!)
Describe Mumps
- Type of virus:
- Envelope:
- Nucleic acid:
Mumps
- Type of virus: Paramyxovirus (close relative of measles
- Envelope: Enveloped
- Nucleic acid: ss(-)RNA
What are the key surface proteins on influenza virus?
- Hemaglutinin (HA)
- Viral receptor binding protein
- Neuraminidase (NA)
- Cleaves host sialic acid to release new virions from host nucleus
Together these protiens are used for serotyping influenza (ex: H1N10)
Which virus is the most common cause of acut gastroenteritis in the USA?
Norovirus
Describe Parvovirus B19
- Type of virus:
- Capsid:
- Envelope:
- Nucleic acid:
Describe Parvovirus B19
- Type of virus: Parvoviridae
- Capsid: Icosahedral
- Envelope: Non-enveloped
- Nucleic acid: ssDNA
Describe Herpesviruses
Family:
Capsule:
Envelope:
Nucleic acid:
Size:
Herpesviruses
Family: Herpes
Capsule: Icosahedral
Envelope: Enveloped
Nucleic acid: dsDNA
Size: Large! >100,000 base pairs
Describe Respiratory Syncytial Virus (HRSV)
- Type of virus:
- Capsid:
- Envelope:
- Nucleic acid:
Respiratory Syncytial Virus (HRSV)
- Type of virus: Paramyxovirus
- Capsid: Helical
- Envelope: Enveloped
- Nucleic acid: ss(-)RNA
How does HIV adhere to and enter host cells?
Early virus: Infects macrophages
- gp120 on the viral envelope binds to host cell CD4
- CCR5 coreceptor on host macrophage is activated
Later virus: Infects CD4+ helper T-cells
- gp120 on the viral envelope binds host cell CD4
- CXCR4 coreceptor on host T-cell is activated
Viral replication is compatible with cell survival in absence of adaptive responses for __________ and _________
Viral replication is compatible with cell survival in absence of adaptive responses for retroviruses (such as HIV) and hepadnaviruses (such as HBV)
What occurs during the eclipse/replication stage of the viral productive replicative cycle?
- Transcription of viral mRNA
- Synthesis of viral proteins
- Replication of viral genome
Which virus causes 5th disease, characterized by “slapped cheek” appearance?
Parvovirus B19
5th Disease = erythema infectiosum; “slapped cheek apperance”
Which complications are associated with parvovirus B19?
Which groups are most likely to be affected?
- Acute symmetric polyarthropathy
- Higher risk in women
- Aplastic crisis
- People wtih hemolytic anemia (ex: sickle cell disease)
- Chronic Aplastic anemia
- AIDS patients
- Hydrops fetalis
- Fetuses
Describe the clinical manifestations of influenza
- Fever
- Chills
- Cough
- Nasal congestion
- Myalgia
- Headache
Describe Influenza Virus
- Type of virus:
- Capsid:
- Envelope:
- Nucleic acid:
Influenza Virus
- Type of virus: orthomyxovirus
- Capsid: Helical tube
- Envelope: Enveloped
- Nucleic acid: ss(-)RNA; segmented
What occurs beyond the maximal upper size limit of RNA virus genomes?
Replication errors render the virus useless or uncompetitive
How is parainfluenza virus transmitted?
Respiratory droplets or fomites
How are enveloped viruses typically transmitted?
Respiratory, parenteral, sexual routes
How are beta herpes virues treated?
ganciclovir or proganciclovir
What is congenital rubella syndrome?
Who is most likely affected?
Congenital rubella syndrome (CRS) is a complication of rubella that can occur in neonates
It is characterized by cardiac, cerebral, opthalmic, and/or auditory defects
What is the mechanism of action of acyclovir?
Acyclovir inhibits viral DNA polymerase, preventing viral genome replication
- Herpes thymidine kinase phosphorylates acyclovir to acyclovir triphosphate
- Acyclovir triphosphate competes for endogenous deoxyguanosine triphosphates
- Bindind acyclovir triphosphate in the growing DNA transcipt is chain-terminating; viral DNA polymerase is inhibited
In the United States, which virus is the leading cause of vaccine-preventable death in children under 5?
Measles
What is a productive viral infection?
A full viral replicative cycle occurs and viral progeny are produced
What complications can arise from HHV8/KSHV?
Which patients are most likely to have these complicaitons?
- Kaposi sarcoma
- an AIDS-defining illness
- Lesions can be cutaneous and/or visceral
- Primary effusion lymphoma (B-cell lymphoma)
- Multi-centric castleman disease
Which virus is the most common cause of severe respiratory illnesses in newborns?
Respiratory Syncytial Virus (HRSV)
How is herpes zoster virus different from varicella zoster virus?
Varicela zoster = primary infection by VZV = chickenpox
Herpes zoster = reactivation infection by VZV = shingles
In the viral productive replicative cycle, when are most enveloped viruses released from infected cells?
- When they acquire the envelope by budding through plasma membrane
- When they acquire an envelope by budding through an internal cell membrane into a secretory compartment and are secreted from the cell
Describe the clinical presentation of echo virus
Nonspecific fever, rash
Describe the characteristics of the alpha-herpes viruses
- Neurotropic
- Broad host range
- Can infect adults and children
- Can infect immune-competent and compromised
- Highly lytic in cell culture
Suppose you know that a virus has helical symmetry
What is the likely makeup of the viral genome?
ssRNA
What makes a cell resistant to viral infection?
Lacking receptors for viral entry
Which part of rhinovirus does the host immune system react to?
Exterior epitopes of VP1, VP2, VP3 (the proteins that make up the viral capsid
What is the relationship between genome size and error rate in replication for viral genomes?
Inversely related
(smaller genome associated with higher error rate)
How is measles prevented?
Measles vaccine!
How is rubella treated?
Supportive care
No antiviral is available
Describe antigenic shift
- Major changes due to gene re-assortment
- Only occurs in influenza A
- Creates new H and/or N combinations
- Causes pandemics
- Ex: H1N1 = re-assortment of 5 different flu viruses, incuding, human, avian, and swine
How are HSV viruses diagnosed?
Tzank prep (look for multinucleated giant cell) or PCR
Describe the clinical presentation of HHV6 in an adult
Infectious mononuclosis
(Note: HHV6 causes roseola in young children)
(heterophile/monospot test will be negative)
How is SARS-CoV Transmitted?
Bats -> Civets -> Humans
Human - Human
Humans are infected by respiratory droplets
In which populations would hepatitis E infection be most concerning?
Pregnant women
Increased risk of maternal and fetal mortality
List the important herpesviruses, grouped by family
Alpha herpes viruses
- HSV-1
- HSV-2
- VZV
Beta herpes viruses
- CMV
- HHV6
- HHV7
Gamma herpes viruses
- EBV
- HHV8 (KSHV)
Describe Norovirus
Type of virus:
Capsid:
Envelope:
Nucleic acid:
Norovirus
Type of virus: Calicivirus
Capsid: Icosahedral; “cup-like” scalloped border
Envelope: Non-enveloped
Nucleic acid: (+)ssRNA
Describe the emergence of West Nile VIrus
First case: 1937, Uganda
USA: 1999, NYC
What would happen if the cellular processes required for viral replication were inhibited in host cells?
Both infected and uninfected would have essential functions shut off (protein synthesis, nucleic acid synthesis)
This would lead to toxicity
What is SSPE?
Which groups are most likely to experience it?
SSPE = Subacute sclerosing parencephalitis
- A complication of measles
- A chronic, degenerative, neurological disease
- Can cause behavior change, intellectual problems, seizures, blindness, ataxia, and eventally death
- Onset is years after measles occurs
- Most likely to occur in children who were less than 2 years old when they are infected with measles
In which settings do outbreaks of norovirus typically occur?
Anywhere where people are in close contact; the virus is very contagious
- Hospitals
- Schools, childcare centers
- Nursing homes
- Restaurants
- Cruise ships
- Military
What is the exception to the rule that larger genome sizes of DNA viruses are associated with higher fidelity of replication enzymes?
Single stranded DNA viruses (mutation rates can approach those of ssRNA viruses)
What must a virus do to establish latency?
The virus must persist, and latency must be reversible
- Virus must hide from the host immune system
- Within a cell
- Don’t synthesize viral proteins
- Except to induce latency/inhibit apoptosis
- Full viral genome must persist
- If the host cell is replicating, it hooks onto a chromosome so it segregaes properly
What is the treatmetn for dengue fever?
Supportive
Why don’t we develop immunity to they common cold?
There are many causes of the common cold
- Rhinovirus, the leading cause of the common cold, has 150 serotypes
- There is little to no serologic cross-reactivity; even if our immune system is ready to moutn a response against one serotype due to previous infection, we are likely to be infected by another serotype
What would be most concerning about seeing a case of Rubella in your ECMH?
Rubella has been eliminated from the United States
A case of rubella in Chicago would be worrisome for an outbreak
Which viruses might caue hand, foot, and mouth disease?
Coxsackie A
EV-71
What is an arbovirus?
A virus that can be transmitted via insect vector
These viruses have evolved to be able to survive and reproduce in its insect vector
Reservoir for an arbovirus may be human or zoonotic
How is measles treated?
There is no antiviral
Vitamin A can decrease mortality by 50%
What is the clinical presentation of mumps?
- Parotitis: Painful swelling of the salivary glands
- Orchititis: Inflammation of the testicles
- Meningitis or encephalitis
Why are dsRNA viruses uncommon?
dsRNA is a PAMP recognized by pattern recognition receptors in our cytoplasm
Rotavirus is able to be a successful pathogen with dsRNA because the TLP/DLP “hide” the dsRNA from the host detection system
What is post-herpetic neuralgia?
Post-herpetic neuralgia = PHN
- Complication of reactivation of VZV
- Nerve is inflammed or injured
- Pain persists after shingles rash has subsided
What advantages and disadvantages do envelopes confer to virons?
- Advantages
- Greater ability to evade the host immune system
- Can change quickly to evade the host immune system
- Disadvantages
- Susceptible to dessication in the environment
- Typically must be transmitted via direct contace
Why do SARS-CoV and MERS-CoV have relatively high case fatality rates?
Zoonotic viruses like SARS-CoV and MERS-CoV have high case-fatality rates becuase they are new to humans.
The virus hasn’t yet evolved a balance between viral replication and keeping the host alive, resulting in death of the host.
Describe Influenza Virus
- Type of virus:
- Capsid:
- Envelope:
- Nucleic acid:
Influenza Virus
- Type of virus:
- Capsid:
- Envelope:
- Nucleic acid:
How did improved sanitation lead to the 1950’s polio outbreak in the USA?
- Poor sanitation meant earlier exposure to poliovirus
- In young children, polio was often mild or subclinical with no paralysis
- Infected children fully recovered with immunity to the virus
- Better sanitation meant decreased liklihood of exposure in early childhood
- Primary exposure in later childhood leads to more serious polio illness
- Severe illness
- Poliomyelitis more common
What is the clinical presentation of Rubella?
Rubella = German measles
- Typically mild in adults
- Teratogenic in pregnant women
- May cause congenital rubella syndrome (CRS) in neonates
- Rash
- Face first, them moves across body
- Low-grade fever
Describe the pathogenesis of poliovirus
- Virus binds to CD155, a cell surface receptor on host cells
- Binding leads to a conformational change in the capsid
- Internal proteins extend into the capsid and form a pore
- ss(+)RNA passes through the pore
- Ribosomes immediately translate the ss(+)RNA -> polyprotein in the cytosol
- The polyprotein is cleaved by viral proteases with autocatalytic activity
- Subsequent replicaiton leads to host-cell lysis in 4-6 hours, releasing up to 10,000 virions
What complication of Zika virus is most likely to arise in pregnant women?
Vertical transmision -> Microcephaly of infant
Describe the DNA nomenclature for viruses with ssDNA
Similar to RNA nomenclature
The template strand for viral mRNA is complementary (-) to the ssDNA
The coding strand is a copy of the ssDNA (+)
What is the clinical manifestation of Coronavirus?
Coronavirus may present as…
- Common cold (a significant percentage of common colds)
- Bronchitis
- Pneumonia
What are the four possible clinical consequences of viral infection?
- Inapparent infection: acute or persistent without symptoms (JC virus)
- Illness to infection: rapid viral multiplication with extensive cell death (Ebolavirus)
- Illness due to persistent infection: chronic tissue damage (Hep C)
- Cancer: cells become transformed into rapidly dividing cancer cells (HPV)
How is Human metapneumovirus diagnosed?
RT-PCR
What is the clinical presentation of Adenovirus?
Clinical manifestation is very broad; infections can be severe, especially in immunocompromised patients
- Upper respiratory tract infection
- Pneumonia
- Conjunctivitis
- Tonsilitis
- Croup
- Gastroenteritis
- Cystitis
- Meningitis
- Encephalitis
How is EBV treated?
Can it be prevented?
Treatment = supportive
No vaccine is available
How is Hepatitis E transmitted?
How can transmission be prevented?
Fecal-oral route
Vaccine can prevent hepatitis E transmissin, but it is not available in the USA. Hepatitis E is not endemic to the USA, and the vaccine was not profitable
Describe the treatment for HIV
Combination of drugs to combat rapid mutation rate
- 2 nucleoside/nucleotide analogs (inhibit reverse transcriptase)
- 1 integrase inhibitor and/or 1 protease inhibitor
What is the causative agent of roseola?
Which individuals are most likely to be affected?
HHV6; young children (6 mo to 2 yo)
What are the limitations of the flu vaccine?
- Long production time
- Limited capacity
- Moderate efficacy in the elderly and immunocompromised
- May mutate in vaccine production
- No cross-reactivity
Describe Rubella
- Type of virus:
- Capsid:
- Envelope:
- Nucleic acid:
Rubella
- Type of virus: Togavirus
- Capsid: Icosahedral
- Envelope: Enveloped
- Nucleic acid: ss(+)RNA
Which virus causes 50% of the cases of “comon cold” in adults?
Rhinovirus
How is mumps diagnosed?
RT-PCR
VIral culture
Serology (positive IgM ELISA or 4 fold increase in IgG)
Describe the mechanisms of infection and reactivation of HSV
Infection
- HSV replicates in and destroys epithelial cells
- Enters endings of adjacent neurons
- Transport through axons to sensory (dorsal root) ganglia
- Establish latent infection
- LAT = Latency-associated transcript (the only viral protein expressed)
Reactivation
- Some stimulus activates the expression of virual genes
- Production of virus
- Travel to body surface
- Lesion forms at or near the site of primary infection
- Typically mouth for HSV-1, genitalia for HSV-2
Which enteric viruses do not caue gastroenteritis?
- Coxsackie A
- Coxsackie B
- Echo virus
- EV-D68
- EV-71
Would a vaccine against rotavirus be effective? Why or why not?
A vaccine against rotavirus would be effective!
- Vaccine would protect against many serotypes
- Cross-protection
(and one does exist!)
Which herpes viruses can be ocogenic?
EBV
HHV8 (KSHV)
What occurs in the assembly stage of the viral productive replicative cycle?
Virus binds to cell surface through interaction of virion proteins w/ existing cell surface receptor
(Some viruses may recognize more than one receptor, allowing use of different receptors on different cell types or alternate routes of entry into a single cell type)
What is a negative sense single stranded viral RNA?
(How does complare to the host cell?)
ss(-) mRNA is complementary to human mRNA
It must be converted to positive sense RNA by RNA-dependent RNA polymerase (encoded by the viral genome) before translation
Describe the presenation of an HCMV infection in an immune-competent patient
Primary
- Asymptomatic or subclinical mononucleosis
Reactivation
- Mild, general illness
How is West Nile Virus diagnosed?
West Nile Virus IgM in serum or CSF
Which two complications of measles may lead to blindness?
Corneal ulceration
SSPE (blindness can occur as the disease progresses)
In general, DNA viruses are…
- Single or double stranded?
- Circular or linear?
- Icosahedral or helical?
- Replicated in…?
In general, DNA viruses are…
- dsDNA
- Linear
- Icosahedral
- Replicated in the nucleus
What are four important characteristics of latent viral infections?
- No viral genome replication except in concert w/ cell division
- Few, if any, viral proteins expressed
- Those expressed can be non-immunogenic - Compatible with cell survival and normal cell functions (some functions may be altered)
- Reservoir for reactivation of infectious virus
What occurs in the replicative cycle of DNA viruses such as adenoviruses and herpesviruses?
- Replicate in the nucleus (expect poxviruses)
- DNA -> mRNA
- Early mRNA: regulatory proteins, proteins important for DNA replication
- Late mRNA: structural proteins
What is notable about the genomes of DNA viruses?
(In comparison to RNA viruses)
Larger genome sizes (high fidelity of replication enzymes)
What complications can arise from HSV-1?
- Herpetic keratitis
- Treatable, infectious blindness
- Encephalitis
- Fever, focal encephalopathy (CT/MRI will reveal lesions on one side of frontal temporal lobe), personality changes
- Can be fatal
- May occur in primary or reactivation infections if the virus travels to the CNS from the dorsal root ganglia
What occurs in the replicative cycle of retroviruses such as HIV?
- ss(+)RNA does not turn into mRNA
- The virus utilizes viral RNA-dependent DNA polymerase (reverse transcriptase) to convert the ss(+)RNA to dsDNA
- The dsDNA is integrated into host cell genome (provirus)
- Transcription is regulated by the host cell
What are the advantages of segmented genomes?
- Reduce the chance that an error in a single component of the genome will incapacitate the entire genome
- Reassortment confers evolutionary advantages
What are the four characteristics of the genomes of RNA viruses?
- Smaller genome sizes (higher error rate when replicating)
- Maximum upper size limit
- Often exist as quasispecies
- Quasispecies = swarms of viruses of the same species with slightly different genome nucleotide sequence
- Creates a target for natural selection
- Segmented genomes
How is norovirus typically transmitted?
Fecal oral route
Viral particles can be aerosolized by vomiting and toilet flust
Airporn particles can be “ingested” and cause illness
What is the purpose of the disassembly stage of the viral productive replicative stage?
Genome becomes accessible for…
- Translation, if the viral genome functions first as mRNA
- Transcription, if the viral genome must first be transcribed into mRNA
- Genome replication (later)
What are the risk factors for reactivation of VZV?
Reactivation of VZV = Herpes zoster virus = Shingles
Risk factors
- Waning immunity
- Old age
- Immune suppression
- Sress
Which family of viruses exhibits episomal latency?
Herpesviruses (HSV, EBV, VZV, CMV)
What are the 7 most common causes of the common cold?
RIP-RACH (Basicaly what people sound like with a cold?)
- Rhinovirus
- Influenza
- Parainfluenza
- Respiratory syncytial virus
- Adenovirus
- Coronavirus
- Human metapneumovirus
Describe Coronavirus (CoV or HCoV)
- Capsid:
- Envelope:
- Nucleic acid:
Coronavirus (CoV or HCoV)
- Capsid: Helical
- Envelope: Enveloped
- Nucleic acid: ss(+)RNA
What are the goals of HIV treatment?
- Prevent spread of HIV
- Prevent progression of HIV
- Maintain leukopoetic stem cells
- Prevent depletion of CD4+ Helper T-cells
- This will prevent/slow progression to AIDS
The virus will not be completely eliminated from the host
Where do most RNA viruses release their genome during the disassembly stage of the viral productive replicative cycle?
Cytoplasm (as ribonucleoprotein)
How is influenza virus spread?
Respiratory droplets and fomites
- Fomites can survive…
- 5 minutes on skin
- 15 minutes on tissue paper
- 1-2 days on plastic or metal
Productive viral infection is necessary in order for the virus to…
- Generate enough virus to spread to target organs and cause disease
- Transmit disease to others
Which groups are most likely to suffer from complications associated with parvovirus B19?
Parvovirus B19 targets erythrocyte synthesis, so anyone with a shorter than normal red blood cell lifespan is more susceptible to complications.
This includes…
- Persons with hemolytic anemia (ex: sickle cell)
- Persons with AIDS
- Unborn fetuses
Describe the presentation of HCMV in an immunocompromised patient (HIV/AIDS and Transplant)
In general: either primary or reactivation infection can cause colitis, hepatitis, and/or retinitis
HIV/AIDS
- Retinitis/retinopathy
- Polyradicuolopathy
- Pain/weakness/loss of sensation
- Esophagitis
- Colitis
Transplant patients
- CMV syndrome
- Fever, leukopenia, atypical lymphocytosis, hepatosplenomegaly, myalgia, arthralgia
- Interstitial pneumonitis/pneumonia
- Colitis
What is the reservoir for West Nile Virus?
Birds
Would a vaccine for norovirus be effective?
Why or why not?
A vaccine for norovirus would not be effective because…
(Norovirus = No effective vaccine)
- The virus does not establish a good protective immunity in the host
- The virus exhibits a high mutation rate
- Immunity is strain (genotype) specific
- No cross-protection among genogroups
Describe the symptoms of EBV activation in an immune-competent patient
- Viral replication in B-cells or epithelial cells in the oropharynx leads to shedding of the virus in the saliva
- This can occur without apparent disease
Which HIV proteins are important for entry and infection of host cells?
- gp120: Binds to host CD4
- RT: Reverse transcriptase - turns ss(+)RNA into DNA
- IN: Integrase - integrates the DNA transcript into the host genome
- PR: Protease - cleaves viral polyprotein into funcitonal units
Note: Pol is the HIV gene that encodes RT, IN, and PR
Which virus is known to cause an aplastic crisis?
Which groups are most likely to be affected?
Parvovirus B19
The virus can cause aplastic crisis in persons with hemolytic anemia
What is the “hallmark” of herpes viruses?
They are forever; They establish latent infections
- Remain invisible to the host
- Replicates if/when the host cell DNA does
- Viral proteins block apoptosis, but do not exert virulence
- This would give away their hiding spot!
Describe the possible complications of EBV
Non-cancer
- Post-transplant lymphoproliferative disease
- Primary CNS lymphoma
- Oral hairy leukoplakia
- Looks like thrush but doesn’t scrape off
- Non-malignant
Cancer
- Burkitt’s lymphoma (non-Hodgkin lymphoma)
- Hodgkin lymphoma
- Mixed cellularity, lymphocytes depleted
- Nasopharyngeal carcinoma
Which individuals are most likely to have severe infections and complications from HCMV?
Patients who are not fully immune-competent
- Patients with HIV/AIDS
- Transplant patients
- Neonates (congenital CMV infection)
Describe the possible clinical presentations of coxsackie B
- Upper respiratory infection
- Myocarditis/pericarditis/dilated cardiomyopathy
- Meningitis
- Pancreatitis
- Sharp lower chest pain
Describe the capsid and envelope of:
Orthomyxovirus
Helical capsic
Enveloped
Between Zika, Dengue, and Chikungunya…
Which can be vertically transmitted?
Which can be sexually tranmitted?
Vertical:
- Dengue, Chikungunya, Zika
Sexual:
- Zika
Which viruses can be treated with acyclovir or valacyclovir?
alpha-herpes viruses
- HSV-1
- HSV-2
- VZV
What is the most important determinant of the type of cells viruses infect?
Surface glycoprotein
(Must have cell surface receptors for the virus)
How is respiratory syncytial virus diagnosed?
RT-PCR is preferred
Rapid antigen test also available, but false positives are common
Do latent viruses always cause recurrent infections?
No
VZV will only reactivate once to cause shingles
(but other, such as HSV, cause recurrent reactivaiton infections)
What is the prevalence of HSV-2?
1/5 adults are infected
Which virus exhibits proviral latency?
HIV
In a helical capsid, what determines the pitch, diameter, and rigidity of the helix?
What determines length?
Sizes of protein subunits and subunit interactions determine the pitch, diameter, and rigidity of the helix
Size of the viral RNA determines the length
What are the two significant, new coronaviruses?
- SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus)
- MERS-CoV (Middle East Respiratory Syndrome Coronavirus)
- Associated with camels
How do primary and reactivated herpes infections differ in their presentation?
Usually the primary infection is more severe
Which influenza virus is associated with pandemics?
Why?
Influenza A
- Undergoes re-assortment, often of human and avian influenza
- Other types alos possible
- This cause a virus that…
- The vast majority of the world has no immunity to
- Has a reservoir in non-human hosts in which antigenic variation can occur
A patient in your ECMH presents with pneumonia-like symptoms.
You take a full history, and discover that the patient thinks they had mono ~6 months ago. Physical exam reveals lymphadenopathy
What is the most concerning diagnosis that should be on your differential?
HIV
- Acute retroviral syndrome presents with mononucleosis
- Patients who are in the “clinical latency” phase often present with lymphadenopathy, community acquired pneumonia, shingles, and/or cervical dysplasia
How is an HCMV infection treated?
Ganciclovir or valganciclovir
Which virus is associated with kaposi sarcoma?
HHV8 (aka KSHV, Kaposi Sarcoma Herpes Virus)
Why does reassortment of segmented genomes in RNA viruses confer an evolutionary advantage?
Different strains of a virus w/ a segmented genome can shuffle and combine genes and produce progeny viruses that have unique characteristics
Describe Parainfluenza Virus (PIV or HPIV)
- Type of virus:
- Capsid:
- Envelope:
- Nucleic acid:
Paranfluenza Virus
- Type of virus: Paramyxovirus
- Capsid: Helical
- Envelope: Enveloped
- Nucleic acid: ss(-)RNA
Describe the clinical presentation of an HIV infection that has progressed to AIDS
AIDS = CD4+ T-cell count <200/uL or AIDS-defining malignancyis present
Clinical symptoms
- Weight loss
- Unexplained illnesses
- AIDS-defining illnesses:
- Kaposi sarcoma
- B-cell lymphoma
Which enterovirus is associated with large outbreaks affecting children and adults in close communities?
Norovirus
What determinant of pathogenicity of rotavirus causes symptoms in the host?
Describe its mechanism of action
NSP4 is an enterotoxin that causes diarrea
- Required for the development of the DLP
- Secreted as a fragment that binds cell receptors
- Mobilizes intracellular Ca2+
- Stimulates anion (chloride) movement across membranes
- Promotes fluid secretion into the intestinal lumen
- This causes explosive diarrhea
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Why do colds occur more commonly in the fall and winter?
- Back to school = increased contact
- Cold weather = more time indoors = increased contact
- Lower ambient temperatures make the virus happy
Which 3 cancers are associated with EBV?
- Burkitt’s lymphoma (non-Hodgkin lymphoma)
- Hodgkin lymphoma
- Mixed cellularity, lymphocytes depleted
- Nasopharyngeal carcinoma
Describe the structre of rotavirus
Rotavirus has dsRNA that is packaged inside of a triple-layered particle that is resistant ot low-pH
What is the main purpose of early viral gene expression?
Take over host cell machinery
What are the 3 major causes of acute flaccid paralysis?
Poliovirus
Other enteroviruses
West Nile
What is aplastic anemia?
A condition in which your body does not produce enough new blood cells (red or white)
What is postpoliomyelitis syndrome?
Late progression of muscle weakness after recovery from poliovirus
- May be casued by physiologic attrition of motor units with age if the motor units were already less innervated due to an earlier, acute poliovirus infection
What is proviral latency?
Viral genome integrated into DNA of host cell (provirus)
Ex: HIV
What are the two types of single stranded viral genomes?
Positive sense
Negative sense
Where in the body does replication of poliovirus occur?
Why is this significant?
The GI tract
This is significant because virions can be shed in the stool
How is Zika virus transmitted?
Aedes mosquito
Sexual transmission
Vertical transmission mother -> fetus
A patient presents with a fever.
You look inside her mouth, and see the following spots across from her 1st molar.
What is your leading diagnosis?
Measles
These are Koplick’s spots - they are diagnostic of measles
Describe the clinical presentation of West Nile Virus
- 1/5 of infected people develop symptoms
- Flu-like
- 1% of infected people develop complications
- Encephalitis (most common)
- Meningitis
- Acute flaccid paralysis
Describe the clinical presentation of dengue fever
Classic dengue fever
- Severe pain (muscle, joint, bone)
- Nausea/vomiting
- Rash
- Conjunctival ingection
- Leukopenia
- Thromboytopenia
- Hemorrhagic manifestation
Hemorrhagic dengue fever
- Fever
- Sever thrombocytopenia (<100k)
- Increased vascular permeability
- Hemoconcentration
- Pleural effusion or ascites
What is an abortive viral infection?
Viral genes are expressed but infectious progeny do not result.
The host cell probably dies
What are the two most common causes of lower respiratory tract infection in young children?
- Respiratory syncytial virus
- Human metapneumovirus
What are the three uses of analysis of viral nucleic acid sequences (viral genomics)?
- Validates original classification
- Permits studies of evolutionary relationships
- Enables rapid classification of newly discovered viruses
How is respiratory syncytial virus treated?
Supportive care
(Nebulized hypertonic saline is sometimes given, but it may not be effective)
Dengue fever, Zika virus, and Chikungunya fever are endemic to similar regions and may present with similar symptoms.
What would you look for to distinguis between them?
Look at the most prominent symptom
Dengue: Muscle/bone pain
Chikungunya: Joint pain
Zika: Rash
Which herpes virus is associated with oral/labial lesions and can infect a broad host range?
HSV-1, also known as herpes labialis
Describe the pathogenesis of EBV
- Transmisison via saliva
- EBV infects B-cells
- B-cells express EBV antigens
- T-cells mount a response, causing a transient, self-limiting, lymphoproliferative syndrome
- Large cytokine release causes “mono symptoms”
- Large increase in T-cells
- The T-cells target and kill infected B-cells that are expressing EBV antigen
- Resolution of the lymphoproliferative phase occurs when the T-cells have killed off the infected B-cells
- Some infected B-cells persist becasue they didn’t express EBV antigen!
- This is where the latent virus lives
In the clinic, how would you differentiate between mononucleosis caused by HCMV and mononucleosis caused by EBV?
EBV mononucleosis is typically more severe, monospot test will be positive
HCMV mononucleosis may be asymptomatic or subclinical in immune-competent patients, monospot test will be negative
What is the difference between acyclovir and valacyclovir?
Acyclovir and valacyclovir are both antiviral drugs used to treat alpha-herpes viruses
- Valacyclovir is a prodrug of acyclovir
- Valacyclovir has higher bioavailability
Describe the pathogenesis of reactivation of VZV
Shingles
- Waning immunity + stimulus to nerves = reactivation
- Begins as logal, abnormal sensation/tingling/itching
- Sensation progresses to acute pain
- Skin lesions erupt in the dermatome of the infected nerve
- Usually only one dermatome is infected, one additional above or below is possible
- More than this = disseminated HZV (occurs in immunocompromised patients
- Resolution: 2-4 weeks later
Describe the clinical symptoms of norovirus
Lots of vomiting, diarrheal gastroenteritis
Symptoms persis for 24-48h after a 2-3 day incubation period
What are the 5 major targets for antiviral therapy?
- Entry
- Replication
- Proviral integration into the host cell dsDNA
- Polyprotein processing
- Release
What complications can arise from hepatitis A infection?
- Fulminant hepatits
- Necrosis of liver parenchyma, decrease in liver size
- Cholestatic hepatitis
- More severe hepatitis
- Relapsing hepatitis
You suspect your patient has mono, but the monospot has come back negative twice.
What else might be causing the persistent fatigue, fever, and sore throat that this patient is experiencing?
HIV
(HIV should be on the differential for anyone with mono-like symptoms who has a negative monospot)
Describe the clinical presentation of Zika virus
Usually mild
- Symptoms
- Acute onset
- Fever
- Maculopapular rash
- Arthralgia
- Conjunctivitis
- Myalgia
- Headache
- Lasts days - 1 week
- Severe disease is uncommon; case fatality is low
- Complications are possible
- Guillan-barre syndrome
- Infection in pregnancy -> congenital infection
- Microcephaly
What is a positive sense single stranded viral RNA?
(How does it interact with the host cell?)
ss(+) RNA viruses are in the same sense as human mRNA and can be immediately translated by the host cell
What are the four general characteristics of most DNA viruses?
- dsDNA
- Linear
- Icosahedral
- Replicate in the nucleus
What are the steps in the productive replicative cycle?
- Attachment
- Penetration
- Uncoating and disassembly
- Transcription
- Translation
- Replication
- Assembly
- Release from cell
Describe the clinical presentation of HSV-2 in adults
- Genital lesions
- Mollaret’s meningitis
- Benign, recurrent lymphocytic meningitis
In the replication cycle of a DNA virus, what do early mRNAs typically encode?
Regulatory proteins and proteins important for DNA replication
List the 5 major types of viruses
- Orthomyxovirus
- Picornavirus
- Hepadnavirus
- Poxvirus
- Retrovirus
Which virus its the most common cause of acute gastroenteritis in young children?
Rotavirus
(Adults are rarely infected because there is a lot of cross-coverage if you are immune to one serotype)
Why is influenza B associated with epidemics but not pandemics?
Influenza B has no subtype variation; it cannot undergo re-assortment that would cause vastly different phenotypes
- Influenza B does not undergo antigenic shift
- Influenza B does undergo antigenic drift
- These small changes are implicated in the different strains of seasonal flu that are seen every year
- These are epidemics
What kind of viral infection spreads the virus to target organs, causes disease, and transmits the disease to other?
Productive viral infection
What is Palivizumab?
What is it used for?
Who should recieve it?
- Palivizumab (synagis) is a monoclonal antibody directed against respiratory syncytial vurus fusion protein
- It is used to prevent RSV infection (not to treat)
- High risk infants should receive palivizumab
- Premature infants
- Infants with cardiopulmonary disease (especially those on ECMO)
What are some examples of cytotoxic effects of viral products that give the virus a competitive advantage for cellular biosynthetic machinery?
- Poliovirus protease cleaves cell cap-binding protein, inhibiting translation of capped mRNAs (poliovirus is uncapped and efficiently translated due to internal ribosome entry site)
- Herpesvirus protein shuts down splicing of cell mRNAs (most herpesvirus late mRNAs are unspliced)
Vitamin A can decrease the mortality of which viral disease by 50%?
Measles
Which virus is known for its characteristic star shape?
Astrovirus (HAstV)
How is chikungunya virus transmitted?
Aedes mosquito
Vertical transmission mother -> fetus
Describe the patogenesis of a VZV primary infection
Inhalation of respiratory droplets
- Primary viremia (free virus)
- Replication of virus in spleen or liver
- Second degree viremia
- Virus-infected leukocytes cary virus to capillary endothelial cells
- Virus spreads to epithelium
- Characteristic lesions on skin and mucosa (resembles HSV lesions, but more widespread)
- Accompanied by fever, headache
- Virus seeds neurons and/or other cells in peripheral sensory ganglia
- Lifelong latent infection
Which herpes viruses remain dormant in sensory ganglia?
How is this related to their reactivation infections?
HSV1, HSV2, VZV; all of the alpha herpesviruses
All three viruses have the ability to cause some kind of neuropathy upon reactivation
- HSV1 = encephalitis
- HSV2 = meningitis (although this is usually benign)
- VZV = shingles; lesion in one dermatome, may lead to paresis, myelopathy, post herpetic neuralgia
List the steps in the course of an HIV infection in an untreated individual
- Transmission/incubation
- 2-3 weeks
- Primary infection = Acute retroviral syndrome
- Lasts 2-3 weeks
- Primary acute mononuclosis or asymptomatic
- Heterophile/monospot negative
- Clinical latency
- Lasts ~8 years
- No obvious symptoms
- May be more prone to contracting infections
- Lots of virions produced, CD4+ T-cells killed, new ones generated
- Progression to AIDS = CD4+ T-cell count <200/uL or AIDS defining is present
- Lasts ~1.3 years, ends in death
- Immune system has lost its ability to replace the CD4+ T-cells that are infected and killed by the virus
Which broad group of viruses often exists as quasispecies?
What is a quasispecies?
Why are quasispecies important?
RNA viruses
Swarms of viruses of the same species but with slightly different genome nucleoside sequences
Prime target for natural selection
What is the clinical manifestation of human metapneumovirus?
- Lower respiratory tract infection in young children
- (Less severe than RSV)
- Common cold in adults
How is poliovirus transmitted?
Fecal-oral route
Associated with poor sanitation
What are the 3 major types of viral structures?
Icosahedral (nearly spherical)
Helical
Complex
Describe poliomyelitis
What is it?
How often does it develop?
Poliomyelitis is a complication of poliovirus that occurs in <1% of all people infected by poliovirus
Poliomyelitis is an asymmetric, ascending paralysis caused by destriction of neurons in the anterior horn of the spinal cord. This can lead to respiratory insufficiency if it reaches the lungs
Which groups are at highest risk for a severe HRSV infection?
HRSV = human respiraotyr syncytial virus
Groups at risk:
- Premature infants
- Infants with cardiopulmonary disease
- Infants on ECMO
- Immunocompromised individuals
What is the mechanism of action of parvovirus B19?
Parvovirus B19 targets erythrocyte progenitors
- Capsid proteins target blood group P antigen (aka globoside)
- This arrests erythroid precursor development
- The result is the formation of giant, inert pronormoblasts
What are the symptoms of acute flaccid myelitis?
- Sudden arm and leg weakness
- Loss of muscle tone
- Facial weakness or drooping
- Difficulty swallowing or speaking
- Severe: paralysis, respiratory failure, death
What is the site of latency of EBV?
B-cells
How is human metapneumovirus treated?
Supportive care
(There is no antiviral treatment or vaccine for hMPV)
Describe the capsid and envelope of:
Retroviruses
Icosahedral
Enveloped
What do retroviruses use to convert ss(+)RNA to dsDNA?
Viral RNA-dependent DNA polymerase (reverse transcriptase)
What are the four general characteristics of most RNA viruses?
- ssRNA
- Replicate in cytoplasm
- Smaller genome
- Haploid
Which polio vaccine is administerd in the USA?
Why?
Enhanced, inactivated polio vaccine
- Similar to the one created by Salk
- Lower risk of vaccine-associated poliomyelitis
- Wil not mutate to a virulent form (chance of this in live, attenuated oral vaccine)
- Does not shed in feces
- Will not “immunize” others, but also will not infect them
Which virus is the exception to the rule “All DNA viruses are double stranded?”
Parvovirus
(ssDNA)
What converts negative sense single stranded viral RNA to positive sense RNA prior to translation?
RNA-dependent RNA polymerase (encoded by the viral genome)
Viral replication requires factors from which sources?
Both the host cell and encoded by the virus
Factors encoded by the virus are typically translated into proteins that are then used in genome replication
(determined by nature of viral genome and where it is delivered to the cell)
Describe Human Metapneumovirus (hMPV)
- Type of virus:
- Capsid:
- Envelope:
- Nucleic acid:
Human Metapneumovirus (hMPV)
- Type of virus: Pneumoviridae
- Capsid: Helical
- Envelope: Enveloped
- Nucleic acid: ss(-)RNA
