Speaker
Description
Influenza A virus (IAV) infections are still a major burden of mankind. High evolution rates as well as the ability to infect a wide range of hosts leads to seasonal epidemics and occasional pandemics. IAV non-structural protein 1 (NS1) is a multi-functional protein that plays diverse roles during virus replication and has been linked to host adaptation. Currently circulating H1N1 viruses in humans show six amino acid changes compared to the swine origin pandemic (pH1N1) virus, which entered the human population in 2009 and eradicated previously circulating H1N1 viruses. In this regard, NS1 of pre-pandemic H1N1 showed high prevalence of serine (S) at position 205 while pH1N1 exhibits an asparagine (N) at this position. Over the course of adaptation in humans, pH1N1 re-acquired S205 suggesting an important role in host adaptation. Interestingly, we found NS1 S205 to be phosphorylated during pre-pandemic H1N1 virus infection. To analyze the importance of S205 phosphorylation in viral replication and host adaptation, we substituted S205 of a pre-pH1N1 to non-phosphorylatable glycine, aspartic acid to mimic constitutive phosphorylation as well as pH1N1 asparagine. Phosphorylation mutants replicated less efficiently compared to wild type. Furthermore, these mutants showed decreased amounts of viral proteins, which can be attributed to a diminished expression of viral mRNAs. So far, we hypothesize that tight temporal regulation of S205 phosphorylation is needed for efficient viral replication and might be re-gained as determinant of functional evolution during adaptation of pH1N1 to the human host, which will be focus of future studies.
| Choose secondary Session | Virus host cell interaction |
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| Choose primary session | Evolution and Emerging viruses |
