Association Between F Protein And Negative Costimulatory Molecule 2B4 In Chronic HCV Infection

Hepatitis C virus(HCV)is a kind of RNA virus with significant heterogeneity and high variability.Viral infections are prone to chronicity,cirrhosis,and even hepatocellular carcinoma(HCC).To date,no effective preventative vaccine has yet emerged clinically.HCV infection has become a global public health problem.At present,the most effective way to prevent HCV infection is to screen HCV high-risk and susceptible individuals and then find early and treat actively.Therefore,studies on the factors associated with HCV chronic infection,such as host immune factors,biological factors(viral gene mutations),genetic factors and environmental factors,are particularly important.The alternative reading frame protein(ARFP),or F protein,is produced by translocating the nucleotide codons encoding the core protein(HCV Core,Core,and C proteins),which is similar to the Core protein and plays a role in regulating intracellular signal transduction,substance metabolism,apoptosis,and induction of immune responses.2B4,or CD244,belongs to the signalling lymphocyte activation molecule(SLAM)family and is mainly expressed in NK cells,T cells,and granulocytes.Binding to its ligand CD48,2B4 exercises biphasic immune functions of activation and inhibition.To investigate the association of HCV F protein and negative co-stimulatory molecule 2B4 with host immune factors in chronic HCV infection,we used molecular epidemiological research methods and case-control study design.Blood samples were collected from 45 patients with chronic hepatitis patient(CHP)and 20 healthy controls.Peripheral blood mononuclear cells(PBMCs)were isolated and cultured.Specific 2B4 antibodies were used for blocking and enzyme-linked immunosorbent assay(ELISA)was used to detect the expression of interleukin-4(IL-4)and interferon(IFN-?).Proliferation and apoptosis of PBMCs were also detected.The results of immunological experiments showed that before the 2B4 antibody was blocked,the levels of IFN-? and IL-4 secretion in PBMCs of HCV patients were higher than those in the healthy group(P<0.001).The IFN-? levels in the HCV-F(-)group were significantly higher than those in the HCV-F(+)group(P<0.05),while the IL-4 secretion levels were lower in the HCV-F(-)group than those in the HCV-F(+)group(P<0.05).After the 2B4 antibody was blocked,the levels of IFN-? and IL-4 in the healthy group were not significantly changed(P>0.05),and the levels of IFN-? secretion in the chronic HCV patients were significantly higher than those before blocking(P<0.05).IL-4 secretion levels were significantly lower than those before blocking(P<0.05),and the levels in HCV-F(-)group were less than those in HCV-F(+)group.This results suggest that there is a correlation between the F protein and the negative co-stimulatory molecule 2B4 in the regulation of immune signals.In addition,proliferation experiments of PBMCs showed that the relative activity of PBMCs in HCV patients was less than 1,and the relative activity of HCV-F(+)group was both lower than that of HCV-F(-)group(P<0.05)before and after 2B4 antibody blocking.After blocking,the relative activities of HCV-F(+)and HCV-F(-)groups increased(P<0.05).The results suggest that HCV infection can lead to decreased cell proliferation activity and decreased cell viability.The presence of F protein can enhance the inhibitory effect of HCV on cell proliferation.Blockade of 2B4 signaling pathway can alleviate the inhibitory effect of HCV on HCV cell proliferation.This study was based on the genetic background of the Han population in East China.It preliminarily explored and revealed the relevance of the HCV F protein and negative costimulatory molecule 2B4 in the chronicity of HCV infection from the molecular level.For further developing personalized prevention and treatment of HCV infection,it provides theoretical basis and clinical research data,which is of great significance.