Involvement Of Viperin In Prevention Of Intrauterine Transmission Of Hepatitis B Virus

Background:Hepatitis B virus(HBV)infection is a serious public health problem,and affects over 350 million individuals worldwide.Among those chronically infected subjects,over one million die annually from HBV-related diseases including liver cirrhosis and hepatocellular carcinoma.Mother-to-child transmission is responsible for the high prevalence of HBV infection in endemic countries,and intrauterine infection is the most important route for the mother-to-child transmission of HBV.Intrauterine infection of HBV occurs in approximately 5-10%of pregnancies of HBV-positive women,while intrauterine infection was avoided in the majority of cases.However,the mechanisms by which intrauterine transmission of HBV is prevented remain largely unknown.Placenta has been proposed to be the pregnancy-specific component of innate immunity,and recently,it was evidenced that primary placental trophoblasts are more resistant to virus infection than non-trophoblastic cells.For the prevention of intrauterine HBV transmission,the antiviral innate immune system is crucial at the maternal-fetal interface where vertical transmission of virus from maternal blood to the fetus occurs.Natural antimicrobials are key mediators of innate immune system,and viperin is one of the important members of natural antiviral peptides.Objectives:To explore the role of viperin in the prevention of intrauterine infection of hepatitis B virus(HBV)Methods:Placental samples were collected from 7 HBV-positive pregnant women with their infants infected via intrauterine transmission(infected group),30 HBV-positive women with non-infected infants(non-infected group)and 30 HBV-negative women(controls)and the expression of viperin in placenta was analyzed with immunohistochemistry and Western-blotting.The expression of viperin of placental trophoblast cell line Swan71 was determined after exposed to HBV.Results:Viperin was localized to syncytiatrophoblast,and there was a significant difference in placental viperin levels among control,non-infected group and infected group(F=12.824,P<0.001).The expression of viperin was significantly higher in non-infected group than control(P =0.019)and infected group(P<0.001),and viperin expression was significantly lower in infected group than control(P =0.001).The exposure to HBV significantly increased the expression of viperin in Swan 71(P<0.001).Conclusions:Exposure to HBV up-regulates viperin expression in vivo and in vitro in placental trophoblast,and lack of this up-regulation is associated with intrauterine transmission of HBV.