Influenza & RSV
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- What family does influenza belong to?
- Orthomyxovirus.
- Describe the structure of the influenza virion and genome.
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*helical, enveloped capsid
*genome is a (-) ssRNA divided among eight segments which are wrapped by NP - What are the two significant glycoproteins on the surface of the influenza virus? What does each do?
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*HA: mediates attachment to the cell surface via sialic acid receptors
*NA: helps the virus penetrate the respiratory mucus and cleaves sialic acid when the virus leaves the cell - Where in the host cell does the replication of the influenza virus occur?
- In the host cell nucleus.
- What are the M1 and M2 proteins?
- They are channel proteins that allow the influx of H+ into the virion which activates several cellular processes
- What are the three general types of influenza virus? Give a brief description of the epidemiology of each.
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*A - affects humans, swine, and birds; causes pandemics, most severe
*B - affects humans only, especially children; causes epidemics
*C - affects humans and swine; sporadic and least severe - What is antigenic drift? Why is the influenza virus prone to this phenomenon? How does this affect immunity?
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*Slight mutational changes in the viral genome that create new serotypes
*occurs because of the high error rate of the viral RNA pol
*allows evasion of immune response - What is antigenic shift? How does it occur? Why do forms that undergo antigenic shift have the capacity to cause pandemic disease?
- An entirely novel form of the influenza virus created when a single cell is infected by human and animal strains of the virus which then reassort their RNA segments. They are dangerous because there is no pre-existing immunity in the population.
- What are three complications of influenza? What populations are affected by each?
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1.Primary viral pneumonia - elderly
2.Secondary bacterial pneumonia - elderly, immunocompromised, COPD patients
3.Reye's syndrome - children who take ASA - Describe the clinical course of an uncomplicated influenza infection.
- Acute onset of fever, chills, and myalgia that is self-limiting within a few days. Cough may persist due to denuding of respiratory cilia.
- How is influenza transmitted?
- Respiratory droplets and close human-human contact.
- What structure on the influenza virus is most often targeted by neutralizing antibodies?
- The HA protein.
- What is the mechanism of action of amantidine and rimantidine? Against which form of influenza are they most effective? How are they different?
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*they inhibit the M2 channel protein to prevent uncoating
*influenza A
*rimantidine usually has fewer CNS side effects - Where in the body is viral replication initiated?
- In the superficial cells of the respiratory tract.
- From what part of the world have most pandemic strains of influenza arisen? Why is this?
- From Asia because farming practices place swine, avian, and human vectors in close proximity. Similar conditions are emerging in Central and South America.
- What are two neuraminidase inhibitors available for treatment of influenza? When must these medications be started to be at all effective?
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*oseltamivir (Tamiflu) and zanamivir (Relenza)
*within 2 days of symptom onset - What are the 2 kinds of vaccine for influenza? What kind of immunity do these vaccines induce?
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1.Injectable killed virus form that contain HA antigen from the three most prevalent strains
2.Trivalent inhaled live attenuated form
*6-12 month humoral immunity - What family does RSV belong to? Describe its virion and genome structure.
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*paramyxovirus
*helical nucleocapsid surrounded by an envelope
*genome is (-) ssRNA - What glycoprotein does RSV use to bind its receptor on the host cell? What glycoprotein does RSV use to penetrate the host cell membrane?
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*G glycoprotein is used to bind host cell receptor
*F glycoprotein is used to mediate fusion and thus penetration of the host cell membrane - What histological feature is characteristic of RSV?
- The formation of a syncytium (multinucleated giant cells).
- What patient population is most affected by RSV? How is infection manifested in these persons?
- Infants less than 6 months of age present with severe LRT infections with bronchiolitis and pneumonia. Note that immunosupressed persons of all ages may have a more serious course.
- How is RSV spread? Is it seasonal?
- The virus is spread by close contact and respiratory secretions and may survive for several hours outside of the body. Epidemics are usually in the mid-winter to late spring.
- What difficulties have been encountered in the development of a vaccine for RSV?
- It is difficult to elicit a strong immune response in infants because of immaturity of their own immune systems and the presence of maternal antibodies. Also the current vaccine cause a more robust response in subsequent infections.
- How is RSV treated? Are there any prophylactic measure?
- Treatment is mostly suppportiive and symptomatic. Ribavirin has been used with mixed results. Immunoglobulin can be used as a prophylactic measure but there is no vaccine.
- Why are both secretory and serum antibody important in immunity against RSV?
- Secretory IgA helps to prevent the URT from infection while serum antibodies prevent infection in the LRT.