Week3: influenza viruses

Question 1

Genomic organization of influenza virus

Answer 1

GENOME
-single stranded negative sense linear RNA virus
-8 segmented genome for A and B, 7 for C
VIRION
-enveloped particles, quasi spherical
-envelope from host cell plasma by budding

Question 2

Genes and proteins of influenza

Answer 2

GENES/PROTEINS

• PB1/2, PA: polymerase, error prone
• HA: Hemaglutinin
• NP: nucleocapsid
• NA: neuraminidase, cleaves bound silica acid to release virus from infected cells
• M1: matrix protein
• M2: membrane protein, forms membrane channel, facilitates uncoating, HA production
• NS1/2: nonstructural protein, nuclear export protein. Only present during replication

Question 3

Influenza virus replication cycle

Answer 3

1. Binding to silica acid containing receptors, Uses HA protein for binding. virus is endocytosed
2. Fuses with vesicle membrane. M2 . protein pumps acid to acidify endosome and uncoat virus
3. Transcription in nucleus
4. Protein synthesis
5. Replication of genome in nucleus
6. Assembly
7. budding from plasma membrane. Uses NA to cleave sialic acid.

Question 4

Influenza A vs Influenza B

Answer 4

INFLUENZA A
-can affect humans, birds, pigs
-most common and usually causes the most serious epidemics
INFLUENZA B
-milder than A

Question 5

2009 H1N1 Swine flu

Answer 5

• pandemic of Influenza A, 5/8 genomic RNAs were of swine origin
• caused greater disease burden in people younger than 25 than older people
• in animal models, caused more lung damage and can replicate more efficiently in trachea and deep lung compared to seasonal flu.

Question 6

Flu symptoms and complications

Answer 6

SYMPTOMS
-fever, myalgia, headache, malaise, nonproductive cough, sore throat, rhinitis
-children: GIT symptoms, otitis media, myositis, croup
COMPLICATIONS
-exacerbation of underlying pulmonary or cardiac disease
-secondary bacterial pneumonia
-primary influenza viral pneumonia
-neuro syndrome: guillain barre, encephalitis, Reye’s

Question 7

Pathogenesis of influenza virus

Answer 7

1. cytopathic effect caused by viral replication: epithelial tissue loss
   - kills ciliated epithelial cells in URT, desquamation of bronchial or alveolar epithelium
2. Immunopathologic effect caused by host: epithelial tissue damage and systemic flu like symptoms
   - inflammatory response
3. Bacteria super infection: viral infection exposes binding site for bacteria and promotes bacteria adhesion

Question 8

Antigenic drift Vs antigenic Shift

Answer 8

1. Drift
   - error prone RNA polymerases facilitates major genetic changes, esp on HA and NA proteins
   - small mutations
2. Shift
   - segmented genome structure and co-infection lead to genetic reassortment
   - coinfection with animal and human strains can generate very different virus strains
   - can result in Pandemics

Question 9

Treatment of influenza

Answer 9

1. M2 as drug target: only for A. Prevents acidification for HA and preventing uncaring and release of influenza A virus
   - Adamantanes (amantadine and rimantidine): Influenza A has developed resistance to them, not recommended.
2. Neuraminidase (NA) target
   - works for A and B
   - virions are attached via HA to cell membrane gp/glycolipids
   - NA inhibitors prevent cleavage of sialic acid residue, so virus isn’t released from infected cell
   - Zanamivir and Oseltamivir

Question 10

Vaccinations for flu

Answer 10

1. Inactivated vaccines
   - persons >6 months
2. Live attenuated vaccine
   - 5-49 yo. Not for pregnant women. But has higher protection.