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- Title
Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication.
- 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.
- Abstract
Norovirus (NoV) is a leading cause of epidemic acute non-bacterial gastroenteritis, and replicates through virion protein genome-linked (VPg)-primed or <italic>de novo</italic> 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 <italic>in vitro</italic>. 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 <italic>in vivo</italic> and consequently in MNV replication, which can provide a new target of therapeutic intervention for NoV outbreaks.
- Subjects
RNA polymerases; NOROVIRUSES; DNA replication
- Publication
Frontiers in Microbiology, 2018, pN.PAG
- ISSN
1664-302X
- Publication type
Article
- DOI
10.3389/fmicb.2018.01466