Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication

Norovirus (NoV) is a leading cause of epidemic acute non-bacterial gastroenteritis, and replicates through virion protein genome-linked (VPg)-primed or RNA synthesis by RNA-dependent RNA polymerase (RdRp). VPg is a multifunctional protein that plays crucial roles in viral protein translation and gen...

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Published in:Frontiers in microbiology 2018-07, Vol.9, p.1466-1466
Main Authors: Lee, Ji-Hye, Park, Beom Seok, Han, Kang R, Biering, Scott B, Kim, Soo J, Choi, Jayoung, Seok, Jong H, Alam, Intekhab, Chung, Mi S, Kim, Ho M, Hwang, Seungmin, Kim, Kyung H
Format: Article
Language:English
Subjects:
interaction
Microbiology
norovirus
RNA-dependent RNA polymerase
viral replication
VPg
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Summary:Norovirus (NoV) is a leading cause of epidemic acute non-bacterial gastroenteritis, and replicates through virion protein genome-linked (VPg)-primed or RNA synthesis by RNA-dependent RNA polymerase (RdRp). VPg is a multifunctional protein that plays crucial roles in viral protein translation and genome replication. However, the interaction between the RdRp and this multifunctional VPg in NoV replication has been unknown. In this study, VPg derived from murine NoV (MNV) was found to mediate the formation of higher-order multimers or tubular fibrils of MNV RdRp, which led to significantly enhanced polymerase activity . The replication of MNV mutants containing a VPg-binding defective RdRp, based on the crystal structure of an RdRp-VPg(1-73) complex, was completely blocked in a cell culture system. Our data suggest that the interaction between RdRp and VPg plays a crucial role in the multimerization-mediated RdRp activity and consequently in MNV replication, which can provide a new target of therapeutic intervention for NoV outbreaks.
ISSN:1664-302X
1664-302X
DOI:10.3389/fmicb.2018.01466