Understanding Host-Influenza Interactions at the Molecular Level

At this moment in time, the detailed mechanistic examination of host-pathogen systems is still in its infancy (Forst, 2006).

Classical virology has mostly focused on the influenza virus itself and somewhat ignored many complex processes from the host cells. Integrated host-viral interaction information is often unavailable or incomplete from traditional pathway databases. This knowledge though is vital for the understanding of host-influenza virus interactions at the molecular level, and could also lead to the development of new, more effective influenza vaccines or anti-viral drugs.

The complicated interactions between the influenza virus and the host include the effects of the binding of the NS1 protein to host molecules, and the influence of host intracellular molecules on influenza life cycle. The binding of NS1 protein of influenza to host molecules may have multiple results.

These results include the inhibition of host mRNA processing and the inhibition of interferon synthesis. The interaction also causes the inhibition of the molecule eukaryotic translation initiation factor 2-alpha kinase 2 (PKR, also called EIF2AK2). When NS1 binds to host polyadenylation specificity factor 4 (CPSF4) it inhibits the export of host cell mRNAs out of the nucleus.

On the other hand, host intracellular molecules can interact with influenza and play significant roles in the influenza life cycle. These molecules include vacuolar protein sorting 28 homolog (VPS28) and glutathione synthetase (GSH). VPS28 can interact with influenza M1 protein which can lead to a reduction in influenza virus production.

Influenza can trigger various responses to the viral infection in different cell types. For example, upon the infection, influenza A virus may induce apoptosis in cells. Apoptosis means programmed cell death. Influenza A virus may induce apoptosis in cells with various molecules involved, including caspase-1 and tumor necrosis factor (ligand) superfamily member 10 (TRAIL).

The cell type, instead of the virus, determines how a cell will die. Bronchiolar epithelial cells are the prime targets for influenza A virus infection. Excessive inflammation caused by overabundant production of proinflammatory cytokines by airway epithelial cells may be an important factor in disease pathogenesis.

The above examples show that the integration of such network information, from molecular pathways to cellular responses, is necessary to form a systemic view about influenza virus infection. A more complete picture of host-influenza virus interactions is emerging as more studies are completed.

Forst, C.V. (2006) Host-pathogen systems biology. Drug Discov Today. 11, 220-227.

Genetic Mutations and the Spread of Influenza Worldwide

http://www.brighthub.com/science/genetics/articles/15343.aspx