Hepatitis C virus infection downregulates the ligands of the activating receptor NKG2D.
Natural killer (NK) cells are a major component of the host innate immune defense against various pathogens. Several viruses, including hepatitis C virus (HCV), have developed strategies to evade the NK-cell response. In our study, we found HCV infection could trigger DNA damage response by both ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) pathways. Recent reports had revealed that NKG2D ligands (NK cell-activating ligands) were upregulated when a major DNA damage checkpoint pathway was activated. However, here we found that DNA damage response was activated but NKG2D ligands were downregulated upon HCV infection. Further studies showed that the protease NS3/4A of HCV which had been shown relation with immune invasion contributed to the reduced expression of NKG2D ligands. These findings provide a novel insight into the mechanisms evolved by HCV to escape from the NK cell response.
Wen
Chaoyang
C
Beijing Institute of Biotechnology, Beijing, China.
He
Xiang
X
Ma
Hongfang
H
Hou
Ningbo
N
Wei
Congwen
C
Song
Ting
T
Zhang
Yanhong
Y
Sun
Liping
L
Ma
Qingjun
Q
Zhong
Hui
H
D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D016174:Hepacivirus / Q000201:enzymology / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus; C576324:ATM protein, human; C576597:ATR protein, human