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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 de novo RNA synthesis by RNA-dependent RNA polymerase (RdRp). VPg is a multifunctional protein that plays crucial roles in viral protein translation...

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Autores principales: Lee, Ji-Hye, Park, Beom Seok, Alam, Intekhab, Han, Kang R., Biering, Scott B., Kim, Soo J., Choi, Jayoung, Seok, Jong H., Chung, Mi S., Kim, Ho M., Hwang, Seungmin, Kim, Kyung H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046605/
https://www.ncbi.nlm.nih.gov/pubmed/30038601
http://dx.doi.org/10.3389/fmicb.2018.01466
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author Lee, Ji-Hye
Park, Beom Seok
Alam, Intekhab
Han, Kang R.
Biering, Scott B.
Kim, Soo J.
Choi, Jayoung
Seok, Jong H.
Chung, Mi S.
Kim, Ho M.
Hwang, Seungmin
Kim, Kyung H.
author_facet Lee, Ji-Hye
Park, Beom Seok
Alam, Intekhab
Han, Kang R.
Biering, Scott B.
Kim, Soo J.
Choi, Jayoung
Seok, Jong H.
Chung, Mi S.
Kim, Ho M.
Hwang, Seungmin
Kim, Kyung H.
author_sort Lee, Ji-Hye
collection PubMed
description Norovirus (NoV) is a leading cause of epidemic acute non-bacterial gastroenteritis, and replicates through virion protein genome-linked (VPg)-primed or de novo 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 in vitro. 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 in vivo and consequently in MNV replication, which can provide a new target of therapeutic intervention for NoV outbreaks.
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spelling pubmed-60466052018-07-23 Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication Lee, Ji-Hye Park, Beom Seok Alam, Intekhab Han, Kang R. Biering, Scott B. Kim, Soo J. Choi, Jayoung Seok, Jong H. Chung, Mi S. Kim, Ho M. Hwang, Seungmin Kim, Kyung H. Front Microbiol Microbiology Norovirus (NoV) is a leading cause of epidemic acute non-bacterial gastroenteritis, and replicates through virion protein genome-linked (VPg)-primed or de novo 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 in vitro. 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 in vivo and consequently in MNV replication, which can provide a new target of therapeutic intervention for NoV outbreaks. Frontiers Media S.A. 2018-07-03 /pmc/articles/PMC6046605/ /pubmed/30038601 http://dx.doi.org/10.3389/fmicb.2018.01466 Text en Copyright © 2018 Lee, Park, Alam, Han, Biering, Kim, Choi, Seok, Chung, Kim, Hwang and Kim. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Lee, Ji-Hye
Park, Beom Seok
Alam, Intekhab
Han, Kang R.
Biering, Scott B.
Kim, Soo J.
Choi, Jayoung
Seok, Jong H.
Chung, Mi S.
Kim, Ho M.
Hwang, Seungmin
Kim, Kyung H.
Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication
title Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication
title_full Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication
title_fullStr Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication
title_full_unstemmed Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication
title_short Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication
title_sort insight into the interaction between rna polymerase and vpg for murine norovirus replication
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046605/
https://www.ncbi.nlm.nih.gov/pubmed/30038601
http://dx.doi.org/10.3389/fmicb.2018.01466
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