Influenza Virus Replication: How the Flu Spreads Inside Your Cells

Replication Cycle

1. Attachment – Hemagglutinin (HA) binds sialic acid receptors on respiratory epithelial cells.
2. Entry – Endocytosis; low pH in endosome triggers HA conformational change, fusing viral envelope with endosomal membrane.
3. Uncoating – M2 ion channel allows H⁺ influx; ribonucleoproteins (RNPs) released into cytoplasm.
4. Nuclear Import – RNPs enter nucleus (influenza replicates in nucleus, unlike most RNA viruses).
5. Transcription/Replication – Viral RNA-dependent RNA polymerase makes mRNA (capped snatched) and cRNA/vRNA.
6. Assembly – New RNPs + proteins traffic to plasma membrane.
7. Budding/Release – NA cleaves sialic acids; virions exit. NA prevents self-aggregation.

Antigenic Drift and Shift

• Drift – Point mutations in HA/NA → seasonal epidemics.
• Shift – Reassortment of gene segments (human + avian/swine) → pandemics.

Transmission

Respiratory droplets, aerosols, fomites. Annual vaccination matches predicted strains.