Introduction

Hepatitis B virus(HBV)and hepatitis C virus(HCV)infection lead to serious health two viruses share the same transmission mechanism,thus co-infection is very common,particularly in high endemic areas,amongst individuals with a highrisk of parenteral infection[1].The prevalence of HBV/HCV coinfection is approximately 5%?20%in patients whose hepatitis B surface antigen(HBsAg)are positive and 2%?10%in HCV-positive patients[2].A prevalence of overt HBV co-infection in HCV-positive patients was recently reported at 1.4%in the United States[1].

Patients with HBV/HCV co-infection behave differently:accelerates liver disease progression and increases the risk of ratios(HRs)for HCC in cases of HBV/HCV co-infection are 6.7 times greater than in those of HBV mono-infection,and 11.1 times greater than in those of HCV mono-infection[3–5].On the other hand,HCV RNA clearance rate in HBV/HCV co-infection individuals was higher than that in HCV mono-infection patients in 14–21 years[6].

Our previous epidemiological survey [7]showed thatin HBV/HCV co-infected patients,the spontaneous clearance of HCV was associated with the level of HBsAg.In all co-infected patients,HCV RNA levels in those with HBsAg-positive were lower than in those with proportion of HCV RNA clearance in patients with HBsAg-positive was significantly higher than that in patients with HBsAg-negative[8].A large-scale study in uremic patients in southern taiwan indicated that if the serum level of HBsAg was higher than 200 IU/mL,the proportion of HCV RNA clearance was higher than those with HBsAg-negative[9].Spontaneous clearance of HCV RNA was associated with HBsAg(not anti-HBc)[7].In a stepwise logistic regression analysis,HBsAg-positive was the only independent factor significantly associated with negative HCV RNA in anti-HCV-positive participants[8].High HBsAg levels was significant determinants of spontaneous HCV clearance in uremic patients[9].However,the mechanism responsible for the effect of HBsAg on HCV clearance remains unclear

Eyre et al.[10]detected no HBV/HCV interactions in Huh7 cells co-infected with HCV and a recombinant adenovirus vector carrying the HBV suggested that an active immune response may be the major determinant of HCV viral ,HBsAg levels represent the complicated balance between the patient’s immune system,the virus and the transcription product of specific mRNAs[9].Consequently,we speculate that the clearance of HCV is likely mediated by an immunological mechanism that is induced by HBsAg during HBV/HCV et al.[11]reported that in responders to vaccination with HBV,natural killer(NK)cells are effectively activated against have not found reports regarding the mutual influence of HBV and HCV in specific cellular ,we hypothesized that HCV clearance was mediated by HBV induced innate immunity.

NK cells are involved in antiviral activity,both directly through cytotoxic effects and indirectly via the production of immunoregulatory cytokines(e.g.,IFN-γ ,TNF-α,TGF-β,IL-10)[12].NK cell activity is a determinant factor in the outcome of HCV infections[13].Increasing evidence indicates that innate NK cells are involved in HCV spontaneous clearance as part of the innate immune response[14–16].Although the existing data regarding phenotype and function of NK cells in HCV infections remain controversial[17–19],many researchers assume that the effector functions of NK cells are determined by the equilibrium of activating(NKG2D and NKp46)and inhibitory(NKG2A)receptors[20].NKG2D serves as an activating receptor,which itself is able to trigger is reported that the changes in the expression of these receptors may play an important role in the spontaneous clearance of HCV[21–24].Kokordelis et al.[22]found that high expressions of NKG2D and NKp46 are associated with self-limiting course of ,blocking of these NK cell receptors significantly impaired antiviral NK cell receptor transmit inhibitory on NK cells in mice and humans can reduce the ability of NK cells to clear HBV[23].

Given the important role of HBsAg and NK cells in the control of HCV,we analyzed the potential of HBsAg to stimulate innate immune mechanisms to induce the clearance of HCV,using an in vitro co-cultured system.

Methods

Patients

Forty-two patients with chronic hepatitis B(CHB)who were not treated with any antiviral drugs nor immunoregulatory agents,and 16 age-,gender-and BMI-matched healthy people who did not have detectable HBsAg and HCV antibody were included in this consents were obtained from all study conformed to the ethical guidelines of the 1975 Declaration of Helsinki and had been approved by the Ethics Committee of the Peking University People’s participants were negative for antibodies against hepatitis C,hepatitis D,and human immunodeficiency virus and had no other severe history of liver(liver cirrhosis or HCC),autoimmune or malignant diseases.

Cell separation

NK cells were immunomagnetically separated from total peripheral blood mononuclear cells(PBMCs)by depletion of non-NK cells using magnetic-activated cell sorting(MACS)cell separation technology(Miltenyi Biotech,Bergisch Gladbach,Germany).Purified NK cells were cultured in RPMI 1640 medium(Gibco Life Technologies,Gaithersburg,MD,USA)supplemented with 10%fetal bovine serum(FBS,Gibco Life Technologies)and 1%penicillin/streptomycin at 37°C and 5%CO2for 5 purity of NK cell cultures was over 95%.

文章来源：《自然灾害学报》 网址: http://www.zrzhxb.cn/qikandaodu/2021/0105/815.html