H5N1 subtype (taxid:102793)

VIRION

Molecular biology

Enveloped. Usually rounded but can be filamentous. The virions are 80-120 nm in diameter.

GENOME

Segmented ssRNA(-) linear genome, encapsidated by nucleoprotein (NP). Contains 8 segments coding for 12-13 proteins depending on strains. Segments size range from 890 to 2,341nt. Genome total size is 13.5Kb

GENE EXPRESSION

Viral RNA polymerase (PB1, PB2 and PA) transcribes one mRNA from each genome segment. Transcription is primed by cap cleaved from cellular mRNAS by Cap snatching. mRNA are polyadenylated by the viral polymerase stuttering on a poly U track MP and NS mRNA can be alternately spliced, giving rise to mRNA coding for M2 and NEP proteins. PB1 mRNA encode three proteins by leaky scanning: PB1, N40 and PB1-F2 . Pa-X protein is translated by ribosomal frameshift on the PA gene .

ENZYMES

• RNA-dependent RNA polymerase [PB1]
• Cap Snatching endonuclease [PA]
• Neuraminidase [NA]

REPLICATION

NUCLEUS

1. Virus attaches to sialic acid receptor though HA protein and is endocytosed by clathrins in the host cell.
2. endosome acidification induces fusion of virus membrane with the vesicle membrane; encapsidated RNA segments migrate to the nucleus.
3. Transcription of genomic segments by the viral polymerase produces mRNAs that are capped and polyadenylated by the viral polymerase.
4. Replication of genomic segments.
5. High level of M1 protein induces genomes segments export from nucleus by NEP protein.
6. Virus assembly and budding occurs at the plasma membrane.

Host-virus interaction

Innate immune response inhibition

Influenza A virus inhibits the cascade leading to production of interferon-beta by targeting different cellular proteins. NS1 inhibits host RIG-I activation upon recognition of viral RNA, and subsequent induction of IFN-beta expression.

Host protein shutoff

NS1 induces host gene expression shutoff by inducing host mRNA suppression through polyadenlyation inhibition. The viral mRNA are not affected because their polyA tail is generated by polymerase stuttering.