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Full-Text Articles in Medicine and Health Sciences
Structural And Functional Insights Into Influenza A Virus Ns1-Mediated Rig-I Antagonism, Alexander Jureka
Structural And Functional Insights Into Influenza A Virus Ns1-Mediated Rig-I Antagonism, Alexander Jureka
All ETDs from UAB
The influenza virus non-structural protein 1 is well known to antagonize the host innate immune response through its interaction with the innate immune sensor, retinoic acid induc-ible gene I (RIG-I). While the complete mechanism of the NS1:RIG-I interaction remains unclear, we were the first to demonstrate a direct interaction between the NS1 RNA-binding domain (NS1RBD) from the 1918H1N1 influenza virus and the second caspase activa-tion and recruitment domain (CARD2) of RIG-I using NMR. In addition, we also identi-fied that mutation of Arg 21 in the 1918H1N1 NS1RBD to Gln (R21Q) completely abrogated the NS1:CARD2 interaction. Given that CARD2 plays a …
Structural And Functional Insights Into The Influenza A Virus Non-Structural Protein 1 Effector Domain, Alex Kleinpeter
Structural And Functional Insights Into The Influenza A Virus Non-Structural Protein 1 Effector Domain, Alex Kleinpeter
All ETDs from UAB
The influenza A virus (IAV) non-structural protein 1 (NS1) is a highly multifunctional viral protein responsible for antagonizing the type-I interferon (IFN) response to infection. NS1 has therefore been identified as a potentially effective target for the development of novel anti-influenza compounds. Furthermore, it is important to understand the molecular underpinnings driving NS1 function to more effectively elucidate antiviral targets. In this dissertation, we have contributed significant insight into NS1’s potential as an antiviral target, and the structure-function relationships driving its activity in an infected cell. First, we structurally characterized the binding of two known influenza inhibitors (A9 and A22) …