NS1 Protein ‘Hides’ Influenza Virus RNA

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NS1 structureThe non-structural (NS1) protein of influenza A viruses plays a major role in countering host immune defence by limiting production of interferon and also limiting the antiviral effects of IFN-induced proteins. NS1 also directly modulates stages of the virus replication cycle, including viral RNA replication and viral protein synthesis. Researchers at the Baylor College of Medicine have now identified a mechanism whereby NS1 protein from the highly virulent avian influenza strain, H5N1, ‘hides’ the pieces of double-stranded RNA that would otherwise trigger an antiviral response. NS1 is comprised of two domains: an RNA binding domain and an effector domain. X-ray crystallography of full-length NS1 revealed that molecules of the NS1 protein combine to form tiny tubules which sequester viral RNA. The oligomeric organisation allows the residues involved in RNA-binding to face inwards towards a 20Å wide central tunnel. Binding sites for cellular factors, which may help to evade an immune response, were also identified on the surface of the tubules. It is not yet known whether NS1 proteins from other influenza strains also form similar tubules but, if so, it is possible that the disruption of such structures could form the basis for new treatments. The findings have been reported in the November 5th online edition of the journal, Nature.

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