Viruses

Question 1

Define the basic properties of viruses

Answer 1

Submicroscopic, infectious, obligate intracellular parasite. When the genetic material of a virus enters the appropriate host cell, it directs the production of viral specific proteins used to build abundant viral progeny. Genetic material (DNA or RNA) is encased in a protein shell.

Question 2

Viruses’ 3 part strategy for survival

Answer 2

1. They house their DNA or RNA in small proteinaceous particles (capsids) 2. The genome contains all the information to initiate and complete an infectious cycle 3. They establish a relationship in a population of hosts; that ranges from benign to lethal

Question 3

Describe two means of classifying viruses

Answer 3

1. The classical (Linean) system: Viruses grouped according to their shared physical properties (DNA/RNA, capsid symmetry - helical/isocahedral, naked/enveloped, dimensions of virion and capsid) 2. Baltimore system: Based on the Central Dogma: DNA->RNA->protein. All viruses must produce mRNA to decode their genomes, the Baltimore system classifies viruses based on how they produce mRNA

Question 4

List the methods for studying viruses

Answer 4

1. Electron Microscopy 2. Animal Models 3. Sequence Analysis 4. Cell Structure 5. Serology 6. other molecular techniques

Question 5

Understand basic methods for studying viruses

Answer 5

1. Viruses are in the range of 10^-7 to 10^-8 and cannot be visualized with a regular microscope - electron microscopy is necessary 2. Cell culture systems are needed to support virus development in order to study them. 3. The plaque assay is used to quantify the extent of viral replication associated with the amount of cell death in a culture medium 4. Can also quantify using antibody markers

Question 6

Identify the main structural characteristics of virus particles: Capsids

Answer 6

Capsids protect the genome and serve as a specific genome delivery device Capsids assemble from components (capsid proteins) made during infection Viruses have evolved two general forms for packaging their genomes Helical Capsids Icosahedral Capsids Both kinds can be surrounded by a lipid envelope

Question 7

Identify the main structural characteristics of virus particles: Envelope

Answer 7

Lipid bilayers acquired during budding that are imbedded with virally encoded glycoproteins that function in: Entry and compatible host cell determinants Assembly and Egress Evasion from host immune system

Question 8

The standard conventions of viral genomes

Answer 8

mRNA Plus (+) strand: mRNA containing a translatable open reading frame, it is “ribosome-ready”, able to be translated into protein the complementary sequence is the (-) strand DNA minus (-) strand: the DNA from which the mRNA (+) is copied DNA Plus (+) strand: the DNA of equivalent polarity to the mRNA (reads like the DNA copy of mRNA +)

Question 9

7 classes of viral genome configuration

Answer 9

1. dsDNA = double stranded DNA
2. Gapped Circular dsDNA
3. ssDNA = single standed DNA
4. dsRNA = double stranded RNA
5. ss(+)RNA
6. ss(-)RNA
7. ss(+)RNA with DNA intermediate

Question 10

Virus Life Cycle - Eclipse and Latent stages

Answer 10

a. Eclipse Period:Viral adhesion/adsorption and release of genome in host cell, 0-12 hours no virus detectable inside or outside of cell. Time from when the virus infects the cell to the time when replicated virus is detectable intracellularly.
b. Latent Period: Includes the eclipse period, but is the time from virus attachment to the release of new viruses from the cell (0-16 hours). Extracellular release. Viruses do not grow exponentially as bacteria do, rather they are released as a burst, due to the fact they are assembled from preformed components

Question 11

Virus Attachment

Answer 11

Specific binding of virus-protein with cell receptor. Target receptors include: proteins (glycoproteins) carbohydrates (found on glycoprotein or glycolipid) *carbohydrate receptors are less specific than protein b/c the same carb. side chains could occur on many different glycoslated membrane molecules

Question 12

Virus Entry

Answer 12

Typically an energy dependent process. Endocytosis into intracellular vesicles the virus will ultimately have to escape or, Fusion of enveloped viruses with the cellular membrane

Question 13

Events that occur during the latent period

Answer 13

Entry Viral gene expression Translation of viral proteins Virus genome replication Assembly of new viruses Egress (release) of virus from the cell

Question 14

Viral protein expression: DNA viruses

which strand needs to be intact, completely?

Answer 14

Double stranded gap genomes or single stranded genomes transcribe mRNA using the (-) strand, this means that the missing strands/gaps must be filled before the genes can be transcribed - the host RNA polymerase II is fooled into doing this

Question 15

Viral protein expression: RNA viruses

Answer 15

All RNA viruses make use of a unique viral enzyme, RNA Dependent RNA Polymerase (RdRp), to produce mRNA and replicate RNA genomes. (+) stranded mRNA, can be directly translated by cellular ribosomes, and RdRp amplifies copies (-) stranded mRNA and double stranded RNA, (+) sense RNA must be transcribed for translation, this can only be done by a packaged RdRp Retroviruses [(+) stranded RNA viruses with DNA intermediate], prior to gene expression must copy ssRNA into dsDNA via packaged reverse transcriptase, dsDNA then incorporates into host genome and then mRNA is transcribed using host cell RNA pol II

Question 16

Viral mRNA expression strategies

Answer 16

The “one gene, one dogma” principle is altered as viruses maximize coding potential via mRNA changes: nested sets of mRNA splicing ambisense coding RNA editing

Question 17

Viral protein expression strategies

Answer 17

The “one gene, one dogma” principle is altered as viruses maximize coding potential via protein changes: polyproteins IRES elements leaky scanning for AUG suppression of termination codons protein processing/conformational change resulting in new activities

Question 18

Explain the effects of tissue tropism, virulence and host responses on the nature of viral disease.

Answer 18

Tissue tropism: a given virus is likely to infect certain tissues and not others. Tropism and the nature of a viral disease is determined by the access to tissue in which a virus can replicate, receptors required for virus binding and entry, expression of host genes required for virus infection (support virus replication), and relative absence/failure of host defenses. Tropism can drive virus population variants among or within individuals, particularly in viruses high mutation rates.

Question 19

Compare and contrast acute local disease versus acute systemic disease in incubation periods

Answer 19

Acute local: 1-3 days

Acute Systemic: 10-21 days

Question 20

Compare and contrast acute local disease versus acute systemic disease in virus shedding and transmission

Answer 20

Acute local: shedding occurs from the site of initial infection

Acute Systemic: shedding could take place from multiple and/or distant sites

Transmission is affected by the site of replication and release as well as the relative stability of the virus particle in the environment. Enveloped viruses are fragile to environmental stresses whereas non-enveloped viruses are hardier.

Question 21

Compare and contrast acute local disease versus acute systemic disease in host responses - what kinds of antibody are utilized for each? And is re-infection more or less common for each?

Answer 21

Acute local: host fights via secretory IgA, there are many rapidbly mutating serotypes so re-infection is common (common colds)

Acute Systemic: host fights via secretory IgA and IgM, due to systemic infection life-long immunity results (ex: measles)

Question 22

Compare and contrast acute local disease versus acute systemic disease in likelihood of re-infection

Answer 22

Acute local: re-infection common b/c many different rapidly mutating serotypes and the host never develops immunity

Acute systemic: re-infection is not common, due to the systemic nature of the virus the host develops immunity

Question 23

Describe the expected outcome of viral infection and disease in a healthy host versus an immune compromised host, including symptoms, shedding and transmission, and length of primary infection.

Answer 23

Healthy host will have acute disease.

Immune compromised host will have chronic disease. Chronic persistent infections can cause ongoing inflammation and so contribute to tumerogenesis.

Question 24

Detail two differences between persistent and latent infection.

Answer 24

Persistent: virus infections that continue to produce virus over long periods of time

Latent: virus genome is relatively silent, there is little gene transcription in most infected cells, and there is little to no disease in a healthy host for a long time, in many cases for life.

Question 25

List the potential outcomes and types of virus diseases, with the contributing factors.

Answer 25

Acute Local: colds, diarrhea - different serotypes, mutation prone

Acute Systemic: measles, smallpox

Chronic: Rubella in neonate

Latent: VZV in nerves

Slow/Progressive: AIDS, cancer

Question 26

List effects of viruses on infected cells, such as cytopathic effect (CPE), syncytia, growth, apoptosis

Answer 26

CPE=cytopathic effects

1. Innate Cell Damage can result from
   
   • integration of the viral genome
   • induction of mutations in the host genome
   • inflammation
   • host immune responses
2. Direct Cell damage
   
   • nuclear shrinking and membrane change
   • morphological change of vacuoles

Syncytia = viral fusion with cell resulting in multinucleate cell.

Growth

• Once infected with virus the cell can grow develop pathogenesis via
  
  • Transformation of normal cell into tumor cell
  • Lytic infection resulting in destruction of cell
  • Persistent infection and slow release/budding of virus over long periods of time
  • Latent Infections the virus is present but not causing harm, later will emerge likely result in lytic infx
  • Note the cell is either permissive (allows the virus to replicate and use cell machinery) or non-permissive (do not intitally allow support virus replication)

Apoptosis

• some cells sense when they are infected, turn on viral specific gens (ex: interferons) which can signal apoptosis via NK cells

Question 27

Explain the interferon response and “anti-viral state

Answer 27

Infections of cells with viruses induces the production of proteins that are known as interferons because they were found to interfere with viral infection of neighboring cells.

• Type 1: antiviral cytokines transiently produced and secreted within hours of infx
• Type 2: produced only by T and NK cells
• The cells respond to interferons via receptors that signal through the JAK/Stat pathways and control genes whose transcription is regulated by ISREs (interferon stimulated response elements)

The antiviral state is induced by interferons and helps prevent a cell from being infected.

• The cell goes into an optimal state to block viral replication
• Alters transcription of ~ >100 genes
• dsRNA activates many interferon responses
• results in temporary block of cell proliferation, decreased metabolism, potentiates NK cell activity including interferon production (can induce flu symptoms), increases production of antigen presenting molecules (MHC class 1), may lead to apoptosis

Question 28

Distinguish between innate and adaptive anti-viral responses

Answer 28

Innate Immunity is non-specific and immediate, and primes and initiates the adaptive immune system. Include natural barriers and soluble factors.

• Natural barriers: skin, mucus, ciliated, epithelium, gastric acid, tears, bile
• Cells: macrophages, NK cells, neutrophils, dendritic cells, granulocytes
• Soluble factors: interferons, cytokines, complement, chemokines

Adaptive - all viruses encode proteins, these are foreign antigens that can elicit specific/adaptive immune responses. Viral antigens may be found on virions, surfaces of infected cells, debris from infected cells, as peptide fragments bound to host MHC molecules on infected cells or phagocytic cells.

• Humoral Response
  
  • B lymphocytes are the effectors, they produce immunoglobulin specific to the virus
• Cell-mediated response
  
  • elimination of infected cells via T cells recognizing MHC antigens to destroy the cell or secrete cytokines
• Memory and secondary response

Question 29

Compare antibodies produced in primary and secondary responses

Answer 29

Antibodies produced during primary virus infections are usually lower affinity than those produced later, and are often of the IgM isotype (not yet switched). Secondary responses will have a larger variety of antibody types (IgG, IgA, IgM), they will have also selected for more potent antibody types produced by B cells and these will be available so the infx can be delt with more potently initally.

Question 30

List and describe major cell types involved in anti-viral responses

Answer 30

Innate Response Cells: macrophages, NK cells (ADCC), neutrophils, dendritic cells, granulocytes

Adaptive Response Cells: B lymphocytes, T lymphocytes (CTL and T helper), Memory cells

Th1 - preferentiate cell-mediate response and inflammation (CTL cells)

Th2 - preferentiate humoral response (B cell antibody production)

Question 31

Compare the efficacy of antibody versus cell-mediated immunity in the anti-viral response

Answer 31

Innate antibody immunity and adaptive cell-mediated immunity share many of the same effector mechanisms but adaptive cell-mediated immunity is able to target viruses with greater precision.

Innate responses can eliminate a viral infection but typically they prevent the infection from getting worse and then the adaptive immune response resolves the infection.

Question 32

Explain means of virus evasion/manipulation of host defenses by various viruses.

Answer 32

Question 33

Know what a virus is and why it is different than a bacteria

Answer 33

A vrius is an infectious agent that infects other living cells. It is different than a bacteria because:

• it cannot replicate on its own
• it requires host cell machinery for replication
• virus must be cultured in human tissue
  *

Question 34

Understand the basic ways to diagnose a viral infection using laboratory tests

Answer 34

You can look for the actual virus:

1. Culture: Growing the virus in tissue (viruses cannot replicate without a host cell).
2. Antigen: various assays that use enzymatic reactions or immunofluorescence to detect specific antigens (“parts”) of the virus in question (rapid flu test)
3. Polymerase Chain Reaction (PCR): This relies on copying and amplifying a portion of the viral genome. This is a very sensitive and specific test and can be done on many different body tissues: blood, nasal wash, CSF, biopsies of tissues. The results can be qualitative (positive or negative) or quantitative (number of copies/mL). You can look for a host’s immune response to a viral infection by looking for antibodies that are specific for that virus. Preferred method.
4. Enzyme-Linked Immunosorbent Assay (ELISA) is the most common. There are several different ways of doing this, but a common ELISA would:

• Coat the plate with a viral antigen (can be the whole virus or part)
• Incubate the host’s serum on the plate to let the antibodies attach to the antigen on the bottom of the wells
• Then incubate the plate with an antibody that detects the host antibody (a secondary antibody)
• Then incubate the plate with a substrate that will allow visualization of the secondary antibody

Question 35

Know the hallmarks of herpes viruses and the 8 herpes viruses that infect humans

Answer 35

• The hallmark of a herpes infection is that once a host is infected, the host is always infected. The virus establishes latency after infection. A latent virus can become reactivated. A reactivated infection doesn’t always cause disease. Herpes viruses contain double stranded DNA. All have primary, latent and reactivation phases.
• • HHV-1: Herpes Simplex Virus-1 (HSV-1)
• • HHV-2: HSV-2
• • HHV-3: Varicella Zoster Virus (VZV)
• • HHV-4: Epstein Barr Virus (EBV)
• • HHV-5: Cytomegalovirus (CMV)
• • HHV-6: Roseola (HHV-6a, HHV-6b)
• • HHV-7: Roseola
• • HHV-8: HHV-8

Question 36

For HSV-1/HSV-2 (Herpes Simplex Virus), students will have a basic understanding of: -Primary infection and reactivation infection -Pathogenesis -Diagnosis -Treatment -Prevention

Answer 36

Primary infection, most primary infections are silent - asymptomatic. If symptomatic, lesions 1-3 days after inoculation, fever, dew on a rose pedal (local infx in immune competent pt.), in immune compromised can spread to systemically resulting in encephalitis/hepatitis. Latent infx remains in the sensory ganglia and is reactivated by stressors.

• Transmission of HSV usually occurs through close contact with a person who is shedding virus at a mucosal surface, or in genital or oral secretions.
• **Occupational hazard for doctors, dentists, nurses. **
• Neonatal HSV: serious disease transmitted to an infant perinatally

Reactivation can be silent (asymptomatic shedding), is contagious, 70% of new genital HSV infections are transmitted by asymptomatic reactivation and shedding. Reactivation can be symptomatic but usually not as severe as primary infx, can be provoked by a variety of stimuli: sunlight; stress; febrile illness; menstruation; immunosuppression

HSV-1 and HSV-2 both cause orofacial and genital lesions.The incubation period is 2-12 days, typically ~4 days. Transmission occurs through inoculation from someone who is shedding virus into a mucosal surface or cut of another person.

Diagnosed clinically but can also do Tzanck smear, HSV culture, Direct Flourescent Antigen Stain, PCR of lesions.

Tx: for severe (neonatal, immunecompromised)=IV acyclovir; oral/genital outbreaks = oral acyclovir; prophylaxis for people with frequent outbreaks

Prevention: No vaccine, hand hygiene, avoid contact, wear gloves; prevent reactivation via regular acyclovir in lower dosage

Question 37

For Varicella Zoster Virus (VZV), students will have a basic understanding of: -Primary infection and reactivation infection -Pathogenesis -Diagnosis -Treatment -Prevention

Answer 37

VZV causes 2 clinical syndromes of importance:

• Chickenpox (varicella) = primary infx
  
  • fever, malaise, headache, +/- cough, itchy rash starting on trunk, lesions in stages
• Shingles (zoster) = reactivation infx (always symptomatic)
  
  • itchy/painful dermatomal rash with grouped erythematous vesicles that crust over after ~2 weeks
  • Post-herpetic neuralgia is most debilitating complication

Pathogenesis:

• Transmission primarily respiratory via droplets aerosolized secretions and contact with lesions
• Entry via respiratory tract o spreads to the regional lymphoid system and replicates over the next 2-4 days
• Then causes a primary viremia (4-6 days after inoculation)
• Virus replicates in liver, spleen and possibly other organs causing a secondary viremia
• The secondary viremia spreads viral particles to the skin 14-16 days causing vesicular rash
• **Pregnant women and immunocompomised patients have highe morbidity and moratality **
• VZV remains latent in the cranial, dorsal root and/or trigeminal ganglia
• Is the ONLY herpesvirus that does NOT have asymptomatic viral shedding (reactivation is always symptomatic)

Dx: clinical, dew drops on a rose pedal

Tx: generally none unless immunocompromised

Prevention: Live attenuated varicella vaccine (VAR) - For chickenpox, immune globulin (Varizig) - pooled antibodies Zoster Prevention/Prophylaxis: There is a licensed vaccine, Zostavax (ZOS), it is a live-attentuated Zoster vaccine - For shingles. One dose age 60 and older is recommended by the ACIP. Boosts the immune response to VZV, cell mediated immunity (CMI) to VZV is an important determinant in who is at risk for shingles - it decreases with age, so older people have lower CMI and are at higher risk

Question 38

For EBV, students will have a basic understanding of: -Primary infection and reactivation infection -Pathogenesis -Diagnosis -Treatment -Prevention

Answer 38

Primary Infx:

• 95% of people are infected with EBV by age 40
• infections often occur in childhood and are asymptomatic or cause mild fever, although 40-50% of people get more sever mononucleosis syndrome which is more severe
  
  • Symptoms include: fever, sore throat, swollen lymph nodes fatigue (resolve in 4-8 wks)
  • Physical exam: Exudative tonsillitis, enlarged cervical nodes, splenomegaly, occasionally hepatomegaly
• Transmission via contact with salvia - kissing or sharing utensils/food/drink

Reactivation Infx:

• EBV remains dormant or latent in the nasopharyngeal epithelium and B cells
• Periodically, the virus can reactivate and is commonly found intermittently in the saliva of infected persons
• This reactivation occurs without symptoms of illness in normal individuals

Pathogenesis:

• virus infects nasopharyngeal epithelium, resulting in cell lysis and spread to surrounding tissues (salivary glands, oralpharyngeal lymph nodes)
• Viremia occurs with distribution to the liver, spleen, and infection of B lymphocytes

Diagnosis:

• Often clinical
• Atypical lymphocytes are seen in the peripheral blood smear, and many patients have >10% atypical lymphocytes on the differential
• Monospot/heterophile tests
  
  • Detects presence of antibodies that cross-react and agglutinate horse/sheep/cattle RBCs
• If a definitive diagnosis is needed, EBV serology is done
  
  • Measures the development of antibodies to EBV antigens: EBNA and VCA
  • An IgM antibody response to the viral capsid antigen (VCA) indicates a recent infection
  • An IgG response to the VCA indicates prior infection

Treatment:

• supportively
• steroids if enlarged tonsils threaten airway or severe hepatitis
• immunecompromised pts. try and reinstate immune system

Prevention:

• No vaccine
• Prevent saliva contact with infectious people

Question 39

For CMV, students will have a basic understanding of: -Primary infection and reactivation infection -Pathogenesis -Diagnosis -Treatment -Prevention

Answer 39

Primary Infx:

• Asymptomatic - For healthy people who are infected, there are usually no symptoms or long term consequences but some minor symptoms may include:
  
  • mild febrile illness similar to mononucleosis, swollen lymph nodes, mild hepatitis
• In immunocompromised CMV is serious and can infect organs, causing retinitis and collitis in HIV pts.
• Congenital/birth acquired CMV there are usually no symptoms or long term consequences, but kids who are affected present with low birth weight, hearing loss, skin rash (blueberry muffins spots)

Reactivation Infx:

• virus remains latent in monocytes and lymphocytes
• when reactivated virus appears in saliva and urine, asymptomatic in healthy patients
  
  • still shed in bodily secretions in asymtomatic pts.
• reactivation can infect children (vertical transmission) during birth
• reactivation in immune compromised patients is severe and can lead to non-focal viral syndrome, organ specific infection, mortality

Pathogenesis:

• Infection occurs by contact with infected bodily fluids
• CMV infects the epithelial cells of the salivary gland or the genital tract
• In developed countries 50-80% of people have CMV by age 40

Diagnosis:

• Serology (CMV IgM and IgG)
• Viral culture
• PCR
• Tissue Histology: infected cells have “owl’s eye”

Treatment:

• No treatment necessary for people with normal immune systems
• Immunocompromised:
  
  • gancyclovir or valganciclovir

Prevention:

• No vaccines available
• Immunocompromised are at a very high risk for severe CMV disease:
  
  • CMV-IG is given once a month as prophylaxis
  • Ganciclovir or valganciclovir used in certain insdtances to prevent disaese (ex: post-transplant)

Question 40

For CMV, understand the significance of infection during pregnancy including features of congenital CMV

Answer 40

• Most common in utero infection in US
• When a pregnant women develops a primary CMV infection, there is a 3-5% chance that the child will be born with a congenital CMV infection
  
  • 2/3 of the infants will not be infected in utero
  • 1/3 of the infants are infected in utero
  • Most infected infants will be asymptomatic
  • Only 10-15% of the infected infants will have symptoms at birth (this is about 3-5% of the infants born to mothers with primary infections)
• Infection of the fetus can also occur if a pregnant women reactivates CMV, but the risk is much lower (<1% of babies will become infected and even fewer are symptomatic)

Congenital CMV syndrome:

• Low birth weight
• Microcephaly
• Hearing loss
• Mental impairment
• Hepatosplenomegaly
• Skin rash (blueberry muffin spots)
• Jaundice
• Chorioretinitis

Question 41

For EBV, know that it is implicated in several types of cancers

Answer 41

Not understood how EBV causes these cancers

• Burkitt’s lymphoma
  
  • Endemic in Africa, occurs sporadically around the world
  • B cell tumor mainly affecting the jaw (abdomen in immunocompromised)
• Hodgkin’s lymphoma
• Nasopharyngeal carcinoma
  
  • Highest incidence seen in Chinese (diet and genetics)
• Lymphoproliferative disease
  
  • Seen in immunocompromised patients
  • Uncontrolled proliferation of EBV infected B cells

Question 42

Describe the pathogenesis and the clinical manifestations of Respiratory Syncytial Virus (RSV) infection in young children

Answer 42

Pathogenesis:

• The RSV virus is enveloped and has ssRNA genome
• Transmission: spread by contact with droplets (respiratory secretions) on environmental surfaces or objects
• Virus enters through mouth and nose resulting in localized infection of the respiratory tract

Clinical Manifestations:

• Primary infection is usually symptomatic and lasts 7-21 days
• Causes acute respiratory disease in patients of all ages
  Bronchiolitis: children <1 yr of age
  Viral pneumonia: young children and the elderly
  Upper respiratory tract infection: children and adults
• In young children and premature infants, RSV is the most frequent cause of bronchiolitis and viral pneumonia
  
  • Wheezing in child <2 yr of age is most likely bronchiolitis

Infants at high risk for severe RSV bronchiolitis

• Premature infants (< 32 weeks gestation)

Treatment:

• mostly supportive

Ribavirin is the only antiviral available for treatment of RSV

• Not recommended for normal hosts
• Currently used in limited and usually dire circumstances (bone marrow transplant, complicated congenital heart disease, etc)
• Efficacy and safety are controversial
• Modest effects in studies
• Drug is given as an aerosol
• Expensive

Prevention:

• No vaccine available

Question 43

Describe the pathogenesis of rotavirus and the clinical manifestations of the disease

Answer 43

Basics

• Rotavirus is a diarrheal disease
• Double stranded RNA virus with a segmented genome
  
  • Allows for reassortment  genetic diversity
• **Leading single cause of severe diarrhea and/or gastroenteritis in infants and young children worldwide
  Globally, rotavirus **

Pathogenesis:

• Fecal to oral transmission
• INfects the epithelial cells (enterocytes) in the ileum

Clinical

• Symptoms: Fever, Vomiting followed by Diarrhea and Abdominal pain

Treatment

• supportive

Prevention

• There are 2 oral, live-attenuated rotavirus vaccines licensed for use in infants
  
  • RotaRix (2 doses): monovalent human
  • RotaTeq (3 doses): pentavalent human-bovine reassortment

Question 44

Recall the basic structure, important elements (including Neuraminidase, matrix protein, and Hemagluttinin) and basic nomenclature of influenza viruses

Answer 44

a. Single stranded RNA virus.
b. Genome is composed of 8 “negative-strand” RNA segments.
c. 2 glycoproteins are important in virulence:

• i. Hemagglutinin –important in virus entry into cell (binds to sialic acid).
• ii. Neuraminidase—important in virus exit from cell.
• iii. Many types of hemagglutinin and neuraminidase-these are designated by numbers.
• Hemagglutinin type is designated by the letter “H”.
• Neuraminidase type is designated by the letter “N”.
  
  • Together these designate the virus subtype (example H3N2).
• Notice that H and N are the main influenza antigens that the immune system recognizes.

d. Matrix protein- matrix proteins are proteins that link the viral envelope with the viral core. M2, an antiviral target, is a proton channel protein that triggers release of the genome into the cytoplasm under acidifying conditions in the endosome.

Question 45

Influenza Nomenclature

Answer 45

Question 46

Understand antigenic drift (point mutation) and antigenic shift (reassortment of genome segments). Antigenic drift does NOT change the subtype of the virus (i.e. H2N2).

Answer 46

• Minor change in the influenza virus caused by a point mutation, same subtype of virus.
• Drift tends to slightly change the presented H/N antigens (just enough that the immune system doesn’t recognize the virus as something it’s seen before).
• Shift radically restructures the viral genome (as when two types of flu virus that have infected the same host cell mix their genomes together by swapping genome segments).
• By convention, antigenic drift does NOT change the subtype (‘named type,’ ie. H2N2) of the virus.

Question 47

Describe how antigenic shift occurs and the role that other species play in generation of pandemic strains.

Answer 47

Antigenic shift is a large mutation or reassortment of genes between different viral strains that results in functional or phenotypic change. New subtype of virus.

i. Results from 2 different species of influenza virus infecting the same cell.
ii. Pigs are a potential mixing vessel (they have receptors for human and avian influenza).
iii. If pig cells are co-infected with an avian strain and a human strain, RNA segments could reassort to produce novel virions that can infect humans.
iv. Novel virions might be so different than previously circulating strains that humans have no prior immunity to them=pandemic.

Question 48

Understand the origin of Pandemic H1N1, the basic epidemiology and morbitidy/mortality - and that it has caused a human pandemic.

Answer 48

Basically right now we’re waiting for H5N1 or one of its ilk to adapt for efficient human-to-human transmission.

Question 49

Know basic principles of influenza vaccines including the differences between the types of vaccine, who can receive them, and what populations should not receive certain types of vaccine.

Answer 49

a. Made yearly based on predictions of circulating strains.
b. 2 types of vaccines are available:
i. Live, attenuated vaccines—administrated intranasally.
ii. Killed vaccines—administered intramuscularly.

Both are called “trivalent”- 2 A types and 1 B type included in every yearly vaccine.

c. Know which vaccine can be given to pregnant or immunocompromised persons (killed vaccine) and which vaccine should only be given to those populations if benefit outweighs risk (live vaccine).
d. Know that the current influenza vaccines provide no protection for the H5N1 strain

Question 50

Know effective influenza prevention strategies.

Answer 50

a. Annual vaccination
b. Cover your mouth if you sneeze or cough
c. Wash your hands—the most effective strategy

Question 51

Describe CDC recommendations on who is recommended to receive influenza vaccine.

Answer 51

“High-risk” group:
All children to 5 years
All healthy adults over 50
People 5-50 with immune problems, diabetes, cancer, pulmonary diseases, etc.
Pregnant women

&

Household contacts of high-risk people
Health care workers

Question 52

Understand what qualities are necessary in a virus strain to potentially cause a pandemic (new gene segment from another species or ability of a nonhuman strain to bind to human receptors), stages of a pandemic, and stages leading up to a pandemic

Answer 52

Pandemic Criteria—How Do You Determine When a Pandemic is Occurring?

Three conditions must be met to define when an influenza pandemic is occurring:

1. Emergence of a new influenza subtype
2. The virus must infect humans and cause serious illness
3. Virus must have sustained human-to-human transmission and spread easily (without interruption) among humans.

Question 53

Discuss avian influenza including the type (H5N1), where it is occurring and contrast it with Pandemic H1N1 in terms of amount of disease it has produced.

Answer 53

All of the above criteria were met by the “swine influenza (Pandemic H1N1)” strain in 2009-2010 and at that time WHO has issued an announcement of an ongoing pandemic. With avian influenza (H5N1), 2 of the 3 pandemic criteria have already been met (by H5N1). Avian influenza has caused human disease on only a very limited basis and to date there has not been sustained human-to-human transmission and spread (therefore condition 3 has not been met).

Question 54

Recognize the important history, symptoms, physical examination signs, and laboratory parameters in a clinical case that help predict whether a patient has a viral infection, bacterial infection, or viral infection with a bacterial complication.

Answer 54

Viral suggestion:

Infection of the respiratory tract: nasopharynx, trachea, upper respiratory tract mostly

Symptoms:

• Neonates: High fever, lethargy, decreased eating, mottling, apnea
• Infants/Toddlers: GI symptoms, fever, anorexia, respiratory symptoms, malaise, headache, sore throat
• Children/Teens/Adults: Rapid onset, high fever, cough, chills, muscle aches

Normal WBC, ESR, CRP

Known exposure in community with history

Non-productive cough

more acute illness

Reasons suggesting bacterial infection:

History that only suggests one infectious process

• Short history of only 2 days
• No variation in symptoms (there was no period where the patient is improving and then abruptly worsened as you might see if a bacterial complication developed following a viral process)

The degree of illness and labs favor a bacterial process

• HIgher temperature with fever than viral (>103), tachycadia, low blood pressure, signs of infx, productive cough
• High WBC, left shift, high ESR, high CRP

Bacterial infections typically cause more severe illness than viral respiratory illnesses

Higher temperature with fever is more likely bacterial

Growth of bacterial cultures

Question 55

Describe the clinical relevance of nucleoside and nucleotide analogs being prodrugs that require intracellular activation plus intracellular vs plasma half-life of active drug

Answer 55

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