VHL negatively regulates SARS coronavirus replication by modulating nsp16 ubiquitination and stability

Xiao Yu; Shuliang Chen; Panpan Hou; Min Wang; Yu Chen; Deyin Guo

doi:10.1016/j.bbrc.2015.02.097

VHL negatively regulates SARS coronavirus replication by modulating nsp16 ubiquitination and stability

Biochem Biophys Res Commun. 2015 Apr 3;459(2):270-276. doi: 10.1016/j.bbrc.2015.02.097. Epub 2015 Feb 28.

Authors

Xiao Yu¹, Shuliang Chen², Panpan Hou¹, Min Wang², Yu Chen¹, Deyin Guo³

Affiliations

¹ College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
² School of Basic Medical Sciences, Wuhan University Wuhan, 430072, PR China.
³ College of Life Sciences, Wuhan University, Wuhan 430072, PR China; School of Basic Medical Sciences, Wuhan University Wuhan, 430072, PR China. Electronic address: dguo@whu.edu.cn.

Abstract

Eukaryotic cellular and most viral RNAs carry a 5'-terminal cap structure, a 5'-5' triphosphate linkage between the 5' end of the RNA and a guanosine nucleotide (cap-0). SARS coronavirus (SARS-CoV) nonstructural protein nsp16 functions as a methyltransferase, to methylate mRNA cap-0 structure at the ribose 2'-O position of the first nucleotide to form cap-1 structures. However, whether there is interplay between nsp16 and host proteins was not yet clear. In this report, we identified several potential cellular nsp16-interacting proteins from a human thymus cDNA library by yeast two-hybrid screening. VHL, one of these proteins, was proven to interact with nsp16 both in vitro and in vivo. Further studies showed that VHL can inhibit SARS-CoV replication by regulating nsp16 ubiquitination and promoting its degradation. Our results have revealed the role of cellular VHL in the regulation of SARS-CoV replication.

Keywords: Replication; SARS-CoV; Ubiquitination; VHL; nsp16.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chlorocebus aethiops
Exoribonucleases / genetics
Exoribonucleases / metabolism
Host-Pathogen Interactions / physiology
Humans
Methyltransferases / chemistry
Methyltransferases / genetics
Methyltransferases / metabolism*
Protein Stability
Proteolysis
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Severe acute respiratory syndrome-related coronavirus / genetics
Severe acute respiratory syndrome-related coronavirus / physiology*
Two-Hybrid System Techniques
Ubiquitination
Vero Cells
Viral Nonstructural Proteins / chemistry
Viral Nonstructural Proteins / genetics
Viral Nonstructural Proteins / metabolism*
Virus Replication / physiology
Von Hippel-Lindau Tumor Suppressor Protein / genetics
Von Hippel-Lindau Tumor Suppressor Protein / metabolism*

Substances

Recombinant Fusion Proteins
Viral Nonstructural Proteins
Methyltransferases
Nsp16 protein, SARS virus
nsp14 protein, SARS coronavirus
Von Hippel-Lindau Tumor Suppressor Protein
Exoribonucleases
VHL protein, human