Hepatitis B Virus, Hepatitis C Virus Infection Influence The Ligands Of The Activating Receptor NKG2D

Many viruses are now known to activate the ATM/ATR DNA damage response, and the level of NKG2D ligands was upregulated by difference methods induce DNA damage response. NKG2D ligands are the ligands of activating receptors of Narural killer (NK) cells. NK cells are a substantive type of lymphocytes that have an important role during the early. Now, research showed that many viruses inhibited the innate immunity by inhibiting the expression of NKG2D ligands of host cells. In addition, the NKG2D ligands which were activated persistently also were recogenised by NK cells, which may lead to cellular damage.Here we showed that the statue of DNA damage response, the cellular aboundance of NKG2D ligands level in reponse to HBV or HCV infection by Western blot, FACS and Dual-luciferase Reporter Assey System.Our previous studies showed that HBV infection activates and exploits ATR DNA damage response to replication stress, and the DNA damage response inhibitor caffeine can inhibit the DNA damage response and the replication of viruses. Here we showed that the level of MICA was upregulated by HBV infected, and the expression of MICA was inhibited when the cell was treated by caffeine. The level of NKG2D ligands transcription was upregulated by HBV infection.Here we showed that HCV infection can induce the DNA damage response, Hepatitis C virus infection induced increased steady state of ATR and ATM protein, ATR and ATM foci formation and phosphorylation of multiple downstream targets including Chk1, p21 and H2AX, as well as prolonged S and G2-M phase duration. In addition, the level of MICA was downregulated but the level ULBP2 kept unchanged upon HCV infection. According to report, NS3/4A protease play an important role in immune response which was induced by HCV. In according with this, we found that the level of protein and transcription level of MICA was downregulated but the transcription level of ULBP2 kept unchanged in the presence of NS3/4A.In summary, we propose that HBV upregulate the express of MICA by inducing ATM dependent DNA damage response. Furthermore, HCV downregulate the expression of MICA by NS3/4A protease. Our results may provide important findings on the mechanism of HBV and HCV persistent infection.