Viruses Flashcards
What are the steps in the productive replicative cycle?
- Attachment
- Penetration
- Uncoating and disassembly
- Transcription
- Translation
- Replication
- Assembly
- Release from cell
Where do most RNA viruses release their genome during the disassembly stage of the viral productive replicative cycle?
Cytoplasm (as ribonucleoprotein)
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)
What converts negative sense single stranded viral RNA to positive sense RNA prior to translation?
RNA-dependent RNA polymerase (encoded by the viral genome)
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
What is the relationship between genome size and error rate in replication for viral genomes?
Inversely related
(smaller genome associated with higher error rate)
Give 2 examples of viral proteins mediating attachment during the attachment stage of the viral productive replicative cycle
- Influenza - hemagglutinin
- HIV - gp120 (outer envelope protein)
Give 2 examples of viruses utilizing existing cell surface molecules in the attachment stage of the viral productive replicative cycle
- Influenza - sialic acid oligosaccharides
- HIV - CD4, CXCR4, CCR5
What do ss(–)RNA viruses use to convert ss(–)RNA to mRNA and genomic ss(+)RNA?
Viral RNA-dependent RNA polymerase
In the replication cycle of a DNA virus, what do early mRNAs typically encode?
late mRNAs?
early: regulatory proteins and proteins important for DNA replication, to take over host cell machinery
late: structural proteins
What do retroviruses use to convert ss(+)RNA to dsDNA?
Viral RNA-dependent DNA polymerase (reverse transcriptase)
What is the most important determinant of the type of cells viruses infect (tropism)?
Surface glycoprotein
(Must have cell surface receptors for the virus)
What is episomal latency?
Extrachromosomal viral genes floating in the cytoplasm or nucleus
Herpesviruses (HSV, EBV, VZV, CMV)
Which family of viruses exhibits episomal latency?
Herpesviruses (HSV, EBV, VZV, CMV)
What is proviral latency?
Viral genome integrated into DNA of host cell (provirus)
Ex: HIV
- An epidemic of gastroenteritis is traced to a malfunction at a local water treatment plant. A viral pathogen is identified. What can you likely predict about this virus?
It is likely a non-enveloped virus
What is the most common viral infective agent in humans?
Rhinovirus
Human rhinovirus is a [family, genetic material/sense, shape, portion of virus]
Human rhinovirus is a picornavirus that has (+)ssRNA and an icosahedral capsid
How does rhinovirus cause rapid onset of infection?
- Rhinovirus adheres to surface receptors within 15 minutes of entering respiratory tract
- Binds to ICAM-1 receptors on respiratory epithelial cells -> infected cells release cytokines and chemokines -> activate inflammatory mediators -> upper respiratory epithelial cell lysis
What is the optimal temperature for replication of rhinovirus?
Where is this temperature found?
32oC
Nose and large airways
Human Metapneumovirus is [family, genetic material/sense]
Human Metapneumovirus is a member of the pneumoviridae family and uses (–)ssRNA
Human metapneumovirus may be the _____ most common cause of lower respiratory tract infection in young children (after RSV) and causes a _____ severe disease than RSV
Human metapneumovirus may be the second most common cause of lower respiratory tract infection in young children (after RSV) and causes a less severe disease than RSV
Human coronavirus is [envelope status, genetic material/sense, shape, structure]
Human coronavirus is an enveloped (+)ssRNA virus that has a helical nucleocapsid
Who is the mortality risk from human parainfluenza virus limited to?
- Very young children
- Elderly
- Immunocompromised
Human adenovirus is [envelope status, genetic material/sense]
Human adenovirus is a nonenveloped dsDNA virus
What allows prolonged survival of human adenovirus outside the body?
Human adenovirus is unusually stable to chemical or physical agents and adverse pH conditions
What illnesses does human adenovirus cause?
URI, pneumonia, conjunctivitis, tonsilitis, croup, gastroenteritis, cystitis, meningitis, encephalitis
What are the symptoms of measles virus?
- Fever
- Cough
- Coryza
- Conjunctivitis
- Koplick’s spots
- Morbilliform rash
Complications of measles are common and most severe in ____. They include:
Complications with measles are common and most severe in adults
They include diarrhea, pneumonia, encephalitis (SSPE: subacute sclerosing panencephalitis), and corneal ulceration leading to corneal ulceration and blindness
What is the clinical presentation of human mumps virus?
Human mumps virus presents with parotitis, orchitis, meningitis/encephalitis (rare)
Rubella is [family, genetic material/sense, envelope status, shape]
Rubella is a togavirus that has (+)ssRNA and an enveloped icosahedral capsid
What is the clinical presentation of rubella?
- Usually mild and subclinical
- Low grade fever
- Rash appearing first on face then moving across body
- Congenital rubella syndrome in neonates (cardiac, cerebral, ophthalmic, auditory defects)
Does rubella still exist in the U.S.?
No, rubella was eliminated from the U.S. in 2004
How are enveloped viruses typically transmitted?
Respiratory, parenteral, sexual routes
How are non-enveloped viruses typically transmitted?
Fecal-oral route
Viruses that can be transmitted through contaminated water are typically non-enveloped
Suppose you know that a virus has helical symmetry
What is the likely makeup of the viral genome?
ssRNA
Describe the clinical manifestations of influenza
- Fever
- Chills
- Cough
- Nasal congestion
- Myalgia
- Headache
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
- Works against influenza A and B
- Alternatives: Zanamivir, Baloxavir
What is Palivizumab?
What is it used for?
Who should receive 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 is the pathogenesis of Parvovirus B19?
- The virus targets erythrocyte progenitors, preventing the synthesis of new red blood cells
- The virus is mild or benign in healthy children
- The 5th disease (Erythema infectiosum)
- “Slapped cheek”
- 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) in fetuses
Vitamin A can decrease the mortality of which viral disease by 50%?
Measles
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
What is rotavirus resistant to?
- Low pH
- Concentrations of chlorine typically used to treat sewage and drinking water
What cell components does rotavirus infect?
Intestinal villi
Where does transcription of rotavirus occur?
Inside the double-layered particle
What does NSP4 of rotavirus do?
an enterotoxin that stimulates anion movement across membranes and promotes diarrhea
What does poliovirus bind?
CD155 cell surface receptor found in humans and some non-human primates
Where does poliovirus replicate?
GI tract
What is the distribution in the severity of symptoms in people infected with poliovirus?
- ~95% have transient viremia
- ~5% have sustained viremia w/ fever, headache, sore throat
- <1% of cases are neuroinvasive
- 0.1% of cases cause frank paralysis
Which viruses cause acute flaccid myelitis?
- Poliovirus
- Non-polio enteroviruses
- West Nile viruses and related viruses such as Japanese encephalitis virus and Saint Louis encephalitis virus
- Adenovirus
Hepatitis A Virus is [family, genetic material, envelope/non]
Hepatitis A virus is a picornavirus that has ssRNA and is nonenveloped
Why can Hepatitis A survive under harsh conditions?
- Resistant to detergent, acid, solvents, drying, high temperatures
- Can survive in fresh and salt water
Why can the Hepatitis A vaccine be given as postexposure prophylaxis?
Hepatitis A has a long incubation period (30 days)
What is the relationship between jaundice and age in people infected with Hepatitis A virus?
Jaundice occurrence increases with age
Describe the important characteristics of Hepatitis E virus
(transmission, incubation, tissues affected, fatality, how to diagnose/treat)
- Fecal-oral transmission
- Common in places with poor sanitation
- Long incubation period (40 days)
- Liver tropism
- No chronic infection
- Overall case fatility rate higher than Hep A (especially high in pregnant women, particularly in third trimester)
- Diagnosed by HEV antibody or HEV RNA
- Effective vaccine developed but stopped b/c not profitable
Which enteric virus generates novel strains by gene segment reassortment?
Rotavirus
During herpesviruses latency, how does the viral genome persist in the cell nucleus?
As an autonomous episome
During herpesvirus latency, how are viral genomes partitioned to daughter cell nuclei of dividing host cells?
Virus expresses EBNA1, which attaches the episomes to cell chromosomes
(examples: B lymphocytes infected with EBV)
What is acyclovir?
A nucleoside analogue used to treat herpesviruses, specifically HSV
What testing can distinguish acute EBV infection from past EBV infection?
Acute EBV infection is often associated with positive heterophile antibody test (monospot), elevated anti-EBV IgM, and a negative anti-EBNA IgG
Development of positive anti-EBNA IgG is correlated with resolution of acute EBV infection
What are the clinical manifestations of CMV infections in immunocompetent vs immunocompromised hosts?
Immunocompetent hosts present with infectious mononucleosis-like syndrome (heterophile mononucleosis)
Immunocompromised hosts typically present with colitis, hepatitis, and retinitis
What are the causes of heterophile-negative mononucleosis?
- False negative (in which case EBV is the cause)
- CMV
- Toxoplasmosis
- HHV-6
- HIV
Which virus has this characteristic “scalloped” border?
Norovirus, of the calicivirus family
Which virus is known for its “wheel-like appearance” en electron micrographs?
Rotavirus
(wheels rotate)
Which virus is known for its characteristic star shape?
Astrovirus (HAstV)
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)
vs norovirus is most common cause of acute gastroenteritis overall
Why is norovirus more likely 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 people 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
What are the most common causes of aseptic meningitis?
Aseptic = viral (no bacteria in CSF)
- Enteroviruses
- Coxsackie A
- Coxsackie B
- EV-71
Which enterovirus can cause an infected individual to require a heart transplant?
Coxsackie B
It can cause severe heart damage
List the important herpesviruses, grouped by family
Alpha herpes viruses (neurotropic, broad host range)
- HSV-1
- HSV-2
- VZV
Beta herpes viruses (slow growing, affect more in immunocompromised, cause enlarged cytoplasm aka cytomegaly)
- CMV
- HHV6
- HHV7
Gamma herpes viruses (oncogenic, lymphotropic)
- EBV
- HHV8 (KSHV)
Which herpes virus is associated with oral/labial lesions and can infect a broad host range?
HSV-1, also known as herpes labialis
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 are the possible complications 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 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
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
Which virus represents the leading causes of congenital mental retardation and hearing loss?
HCMV
What is the site of latency of EBV?
B-cells
Which 3 cancers are associated with EBV?
- Burkitt’s lymphoma (non-Hodgkin lymphoma)
- Hodgkin lymphoma
- Mixed cellularity, lymphocytes depleted
- Nasopharyngeal carcinoma
Describe the clinical presentation of HHV6 in an adult
Infectious mononucleosis
(Note: HHV6 causes roseola in young children)
(heterophile/monospot test will be negative)
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
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
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
How is Dengue fever transmitted?
Aedes mosquito
Vertical transmission from mother to fetus is possible
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 chikungunya virus
- Fever
- Arthralgias
- 60% of infected have persistent joint pain for years
How is chikungunya virus transmitted?
Aedes mosquito
Vertical transmission mother -> fetus
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
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
Dengue fever, Zika virus, and Chikungunya fever are endemic to similar regions and may present with similar symptoms.
What would you look for to distinguish between them?
Look at the most prominent symptom
Dengue: Muscle/bone pain
Chikungunya: Joint pain
Zika: Rash
How is SARS-CoV Transmitted?
Bats -> Civets -> Humans
Human - Human
Humans are infected by respiratory droplets
How is MERS-CoV transmitted?
Bats -> Camels -> Humans
Human - Human
Humans are infected by respiratory droplets
