Influenza Virus

1. Why are influenza viruses important? Give two reasons.

  • Influenza viruses are responsible for significant global disease burden, causing hundreds of thousands of deaths annually.

  • They are capable of undergoing frequent genetic changes (drift/shift), making them highly adaptable and responsible for epidemics and pandemics.

2. To which family and Baltimore class do these viruses belong?

  • Family: Orthomyxoviridae

  • Baltimore Class V: (-) single-stranded RNA viruses

  • Key features:

    • Segmented genome (8 RNA segments in Influenza A)

    • Enveloped

    • Replication occurs in the nucleus, unlike most RNA viruses

3. How many genera are in this virus family? Name them.

  • Three genera:

    • Influenza A virus

    • Influenza B virus

    • Influenza C virus

  • Most studied: Influenza A virus due to its role in pandemics and broader host range (birds, pigs, humans).

4. Describe the structure of Influenza A virion.

  • Shape: Spherical or elongated, enveloped

  • Genome: 8 segments of ssRNA (-), encapsidated with nucleoprotein (NP)

  • Proteins:

    • HA (hemagglutinin): binds to host receptors (HA1 = antireceptor)

    • NA (neuraminidase): cleaves sialic acid to release virions

    • M2 ion channel: acidifies virion interior for uncoating

    • NP (nucleoprotein): stabilizes RNA segments

    • PA, PB1, PB2: RNA polymerase complex (transcription/replication)

    • M1: matrix protein for assembly

    • NS1, NS2: regulate host response and nuclear export

5. Describe the multiplication cycle (step-by-step).

  • Attachment:

    • HA1 binds to N-acetylneuraminic acid (sialic acid) on host respiratory epithelial cells

  • Entry:

    • Virion enters via endocytosis

    • M2 channel pumps protons into virion, uncoating the virus

    • HA conformational change fuses endosomal and viral membranes

  • Uncoating & transport:

    • RNPs released and imported into the nucleus

  • Transcription (viral enzyme):

    • Cap-snatching from host mRNA for initiation

    • mRNA is spliced and exported to cytoplasm

  • Translation (host ribosomes):

    • Viral proteins synthesized

  • Genome replication (viral enzyme):

    • Occurs in nucleus using RNA-dependent RNA polymerase

  • Assembly:

    • RNPs and proteins migrate to the plasma membrane

  • Egress:

    • Virions bud from cell, NA cleaves sialic acid to prevent re-binding

6. What are the target cells for this virus?

  • Human: Respiratory epithelium

  • Avian: Intestinal epithelium

7. Which steps use cellular vs. viral enzymes?

  • Cellular enzymes:

    • Translation (host ribosomes)

    • mRNA processing (used for cap-snatching)

  • Viral enzymes:

    • RNA transcription and replication (via PB1, PB2, PA)

    • NA for virion release

8. What cellular sites are involved?

  • Nucleus: Transcription and replication

  • Cytoplasm: Translation

  • Plasma membrane: Assembly and budding

9. Explain the pathogenesis of influenza virus.

  • Rapid onset of symptoms: fever, headache, muscle pain, cough

  • Virus destroys ciliated epithelial cells → impairs mucociliary clearance

  • Secondary bacterial infections (e.g., pneumonia) may occur

  • Systemic effects due to cytokine production and immune response

10. Why can influenza cause pandemics?

  • Due to antigenic shift, new subtypes with novel HA and/or NA proteins emerge

  • No preexisting immunity in human populations

  • Reassortment occurs in pigs (mixing vessel) when infected with both avian and human strains

11. What is antigenic shift vs. antigenic drift?

  • Antigenic drift:

    • Minor changes due to point mutations in HA/NA genes

    • Responsible for seasonal epidemics

  • Antigenic shift:

    • Major change due to reassortment of RNA segments

    • Causes pandemics (e.g., H1N1 in 2009)

12. How are influenza infections controlled?

  • Vaccination:

    • Inactivated, recombinant, and live-attenuated (FluMist)

    • Annual reformulation due to antigenic drift

  • Antiviral drugs:

    • NA inhibitors: Oseltamivir (Tamiflu®), Zanamivir (Relenza®), Peramivir (Rapivab®)

    • Cap-endonuclease inhibitor: Baloxavir marboxil (Xofluza®)

  • Prevention habits: Hand hygiene, coughing etiquette, disinfection, staying home when sick

13. Why is the vaccine less effective in some years?

  • Mismatch between circulating strains and vaccine components due to unpredictable antigenic drift

  • Production methods (e.g., egg-based) may introduce slight changes affecting immune response