Determinants of the rotavirus NSP1 protein affecting its role as an interferon antagonist

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIAID	VIROL/MICRO-3

* FARE Award Winner

Authors

• M Arnold
• J Patton

Abstract

Rotavirus (RV) is a leading cause of severe childhood diarrhea, annually accounting for approximately 500,000 deaths worldwide. The nonstructural protein NSP1 plays a role in viral spread in the host. To suppress the host interferon (IFN) response, many RVs use NSP1 to induce the degradation of IFN regulatory factors IRF3, IRF5 and/or IRF7. Alternatively, some RVs target a component of the complex responsible for activating NF-kB (b-TrCP). The capacity to target different proteins for degradation is consistent with sequence variation noted among NSP1 proteins, particularly at their C terminus. Despite this variation, all NSP1 proteins share a conserved RING domain near the N terminus formed by a conserved pattern of Cys and His residues, similar to that of some E3 ubiquitin ligases. To investigate the role of the RING domain, the variable C-terminal sequence, and conserved Lys residues in the function of NSP1, we engineered mutant NSP1 proteins and assayed their capacity to degrade IRF3, IRF7 and b-TrCP targets. These studies indicate that despite sequence variability, NSP1 proteins from different strains appear to degrade different host targets via a similar mechanism, with the RING domain facilitating the transfer of ubiquitin moieties onto targets recognized by the C terminus of NSP1.

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