Influenza virus

Type

Enveloped, spherical or rod-shaped, negative-sense ssRNA virus

Virion

Genome

Segmented (8 segments)

Replication site

Nucleus

Outer envelope

• Derived from host plasma membrane

• Contains surface glycoproteins: HA, NA, M2

Haemagglutinin (HA)

Binds to sialic acid receptors; initiates entry; neutralizing antigen

Neuraminidase (NA)

Cleaves sialic acid to release virions; degrades mucin; non-neutralizing antigen

Matrix protein 2 (M2)

Proton channel; aids in uncoating and virion stability

Matrix and core

• M1 protein

• Nucleocapsid

M1 protein

Lines inside of the envelope; supports structure

Nucleocapsid

Each RNA segment is associated with:

• NP (nucleoprotein)

• RNA polymerase complex: PB1, PB2, PA

Virus types

• Influenza A, B, C, D

• Vaccines target A & B

• Subtype naming (e.g., H1N1, H3N2)

  • 18 HA types × 11 NA types = 198 combinations

• Serotypes based on internal proteins (no cross-reactivity)

Replication cycle

1. Attachment:

2. Uncoating

3. Transcription/Replication

4. Assembly

5. Budding

Total replication time ~8 hours

1. Attachment

HA binds sialic acid → endocytosis

2. Uncoating

M2 channel acidifies → viral genome released

3. Transcription/replication

1. RNA segments go to nucleus

   • (–)ssRNA → (+)mRNA → proteins

   • (–)ssRNA → (+)cRNA → new (–)ssRNA

4. Assembly

Viral proteins/segments transported to membrane

5. Budding

NA cleaves sialic acid → virion released

Host Specificity & Pathogenicity

• HA = major determinant

  • Receptor Binding Site:

    • Humans: α2,6 sialic acid

    • Birds: α2,3 sialic acid

  • Cleavage Site: Needed for activation (by protease)

• Pigs: Can host both receptor types → “mixing vessel”

Antigenic Drift (Minor)

• Point mutations in HA/NA

• Due to lack of proofreading

• Causes seasonal flu (epidemics)

• Occurs in A, B, C

Antigenic Shift (Major)

• Reassortment of segments

• Produces new subtypes

• Only in Influenza A

• Requires co-infection, often in animals (e.g., pigs)

Treatment: M2 Inhibitors

• Amantadine, Rimantadine

• Block uncoating

• Influenza A only

• High resistance (>90%)

• CNS & anticholinergic side effects

Treatment: NA Inhibitors

• Oseltamivir (oral), Zanamivir (inhaled)

• Influenza A + B

• Use within 48 hours

• Shorten illness by 1–2 days

• Can be prophylactic

Key takeaways

• HA: Critical for entry & vaccines

• NA: Helps virus exit

• Segmented genome → reassortment (shift)

• No proofreading → mutation (drift)

• Replication in the nucleus

• New flu vaccine yearly due to antigenic drift