Detailed Notes on Influenza Virus Structure and Lifecycle

Orthomyxoviridae Family

  • Influenza (flu) virus belongs to the Orthomyxoviridae family.

  • Characterized by a negative sense RNA genome.

  • Genome is segmented (18 segments) and encodes up to 10 proteins each.

Structure of Influenza Virus

  • Virion Structure: Contains the genome surrounded by viral proteins including:

    • Nuclear Protein: Stabilizes the genome.

    • RNA-dependent RNA Polymerase: Assists in transcription and replication.

    • Composed of three subunits: PA, PB1, PB2.

    • Matrix Protein: Forms the capsid and contains the genome.

    • Enveloped with Lipid Membrane: Contains M2 protein, an ion channel essential for hydrogen ion transport.

    • Spike Proteins:

    • Hemagglutinin (HA): Attachment receptor.

    • Neuraminidase (NA): Release receptor.

Life Cycle of Influenza Virus

  1. Attachment: Hemagglutinin on the viral surface binds to cell surfaces.

  2. Internalization: Endocytic compartment forms upon binding.

  3. Activation of M2 Protein: Pumps hydrogen ions into the virion, lowering pH.

  4. Genome Release: pH drop destabilizes the virion, allowing genome entry into the cytoplasm.

  5. Nuclear Replication: Genome then goes to the nucleus for replication, producing both positive sense and negative sense RNAs.

  6. Production of Viral Proteins: Positive sense RNA is used for protein synthesis, while negative sense RNA is the genome.

  7. Assembly and Budding: New viral particles are assembled and released via the action of neuraminidase.

Reservoirs and Transmission

  • Animal Reservoirs: Aquatic birds from China and Southeast Asia have migratory routes aiding the spread of influenza viruses.

  • Subtypes: Defined by hemagglutinin (HA) and neuraminidase (NA). Examples include H2N2, H3N2, etc. Antibodies show serological distinctiveness between subtypes.

  • Transmission to Other Species: Viruses spill over from birds to mammals and domesticated animals, including poultry and pigs.

  • Human Influenza Subtypes: H1N1 and H3N2 emerged through pandemic outbreaks, establishing as endemic viruses responsible for seasonal epidemics.

Hemagglutinin (HA) Functionality

  • HA forms a trimeric structure with an antigen binding pocket that binds to sialic acid on host cells.

  • Sialic acid is a terminal sugar linked to galactose forming a glycan structure on cell membranes.

  • Linkage Types: (1) Alpha-2,6 (found in humans) and (2) Alpha-2,3 (found in birds).

  • Tropism (species specificity): Different subtypes recognize different sialic acid linkages, influencing infection.

Infection and Replication Specificity

  • Influenza causes localized infections in the lung due to proteolytic cleavage of HA by trypsin-like proteases, which are only present in lung tissue.

  • Proteolytic Cleavage: Necessary for conformational changes of the HA, facilitating viral membrane fusion with host cells.

  • The conformational change exposes alpha helices which bind and penetrate the host cell membrane, creating a pore for genomic entry into the cytoplasm.

Conclusion

  • Understanding the influenza virus lifecycle and the role of its components is crucial for treating and managing outbreaks.