Alphainfluenzavirus (taxid:197911)

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 12-14 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. Some strains can express M42 from the M segment . 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. Leaky scanning may produces N-truncated PA proteins, namely PA-N155 and PA-N182 . PB2-S1 would be an alternative splicing from PB2 gene (unpublished 1/1/15).

ENZYMES

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

REPLICATION

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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 the 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.

Influenza species tropism

It is generally accepted that human influenza viruses preferentially bind to host glycoproteins/glycolipids containing sialic acids in alpha 2,6 linkage, whereas avian influenza viruses bind to those containing sialic acids in alpha 2,3 linkage.

Recent studies have shown that the Human traches and alvoeli epithelial cells are mainly expressing alpha 2,6 sialic acids, when only alveoli are expressing alpha 2,3 sialic acids . This could explain why avian viruses could succesfully infect humans only when breathed at high doses. Indeed the trachea and bronchioles are much easier to reach than the alveoli for aerial-transmitted virus.

These results are debated, and investigations are needed to understand the whole picture .