# 2.3 Genomic diversity of influenza

The genome of flu viruses consists of around 14 000 nucleotides of negative-sense single-stranded RNA. Compare this number to the approximately 3 billion nucleotides found in the human genome or the 150 billion nucleotides of the genome of the marbled lungfish (the largest genome known in vertebrates).

The genome of influenza viruses is segmented, into eight distinct fragments of RNA containing 11 genes and encoding approximately 14 proteins (see Table 1 below). This structure has significance for the spread of the virus and the severity of disease symptoms.

Cases of influenza generally arise in two main ways: by provoking seasonal annual outbreaks or epidemics and, less commonly, through global pandemics. As you will see shortly, both of these phenomena occur as consequences of the fact that the virus uses RNA as its genetic template and that this RNA genome is segmented into discrete strands.

## Table 1 The genome of influenza virus. Note that a single RNA segment may encode for more than one protein due to alternative reading frames.

Gene name | RNA strand (segment number) | Function(s) of protein encoded by this gene
--- | --- | ---
PB2 (polymerase basic 2) | 1 | A subunit of viral RNA polymerase involved in cleaving the cap structure of host cell mRNA and generating primers that are subverted for use in the synthesis of viral RNA.
PB1 (polymerase basic 1) | 2 | Core subunit of viral RNA polymerase. Required for polymerase assembly.
PB1-F2 | 2 | Binds to components of the host mitochondria, sensitising the cell to apoptosis and contributing to pathogenicity.
PA (polymerase acidic) | 3 | A subunit of viral RNA polymerase which also has protease activity of unknown function.
HA (haemagglutinin) | 4 | Antigenic glycoprotein used for binding to (infecting) the host cell.
NP (nucleoprotein) | 5 | RNase resistant protein. Binds viral genomic RNA to form stable ribonucleoproteins and targets these for export from the host nucleus into the cytosol. Also involved in viral genome packaging and viral assembly.
NA (neuraminidase) | 6 | Cleaves sialic acid. Important for releasing viral particles from host cell.
M1 (matrix 1) | 7 | Binds viral genomic RNA and forms a coat inside the viral envelope in virions. Inside the host cell, it starts forming a layer under patches of the membrane rich in viral HA, NA, and M2 and so facilitates viral assembly and budding from the host cell.
M2 (matrix 2) | 7 | Transmembrane ion channel protein. Allows protons into the virus capsid, acidifying the interior, destabilising binding of M1 to the viral genomic RNA which leads to uncoating of the viral particle inside the host cell.
NS1 (non-structural 1) | 8 | Inhibits nuclear export of the host’s own mRNA, thereby giving preference to viral genomic RNA. Blocks the expression of some host inflammatory mediators (interferons) and interferes with T cell activation*.
NS2/NEP (non-structural 2/ nuclear export protein) | 8 | Mediates the export of viral genomic RNA from the host nucleus to the cytoplasm.

* Interferons and T cells are involved in the immune response to pathogens.

- The influenza virus is a successful pathogen because it is constantly changing. How might having a segmented genome promote the evolution of new strains of influenza virus?

- If a cell is infected with more than one strain of virus at the same time, then a new strain can be generated simply by mixing RNA strands from different viruses.

OpenLearn - Influenza: A case study
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