VHL negatively regulates SARS coronavirus replication by modulating nsp16 ubiquitination and stability.
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.
College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
Xiao
X
Yu
School of Basic Medical Sciences, Wuhan University Wuhan, 430072, PR China.
Shuliang
S
Chen
College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
Panpan
P
Hou
School of Basic Medical Sciences, Wuhan University Wuhan, 430072, PR China.
Min
M
Wang
College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
Yu
Y
Chen
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.
Deyin
D
Guo
D000818:Animals; D002522:Chlorocebus aethiops; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D017361:Viral Nonstructural Proteins; D008780:Methyltransferases; C558879:Nsp16 protein, SARS virus; C525596:nsp14 protein, SARS coronavirus; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D005095:Exoribonucleases; C497446:VHL protein, human
Replication; SARS-CoV; Ubiquitination; VHL; nsp16