Posttranscriptional inhibition of class I major histocompatibility complexpresentation on hepatocytes and lymphoid cells in chronic woodchuck hepatitis virus infection

Woodchuck hepatitis virus (WHV), similar to human hepatitis B virus, causes acute liver inflammation that can progress to chronic hepatitis and hepato cellular carcinoma, WHV also invades cells of the host lymphatic system, wh ere it persists for life. We report here that acute and chronic hepadnaviru s hepatitis is characterized by a profound difference in the expression of class I major histocompatibility complex (MHC) molecules on the surface of infected hepatocytes and, notably, lymphoid cells. While acute WHV infectio n is accompanied by the enhanced hepatocyte surface presentation of class I MHC antigen and upregulated transcription of the relevant hepatic genes, i nhibition of class I antigen display on liver cells is a uniform hallmark o f chronic WHV infection. This inhibition in chronic hepatitis occurs despit e augmented (as in acute infection) expression of hepatic genes for class I MHC heavy chain, beta(2)-microglobulin, and transporters associated with a ntigen processing (TAP1 and TAP2), Further, the class I antigen inhibition is not related to the histological severity of hepatocellular injury, the e xtent of lymphocytic infiltrations, the level of intrahepatic gamma interfe ron induction, or the hepatic WHV load. Importantly, the antigen expression is also inhibited on organ lymphoid cells of chronically infected hosts, T he results obtained in this study demonstrate that the defective presentati on of class I MHC molecules on cells supporting persistent WHV replication is due to viral posttranscriptional interference. This event may diminish t he susceptibility of infected hepatocytes to virus-specific T-cell-mediated elimination, hinder virus clearance, and deregulate the class I MHC-depend ent functions of the host immune system. This multifarious effect could be critical for perpetuation of liver damage and evasion of the antiviral immu nological surveillance in chronic infection and therefore could be supporti ve of hepadnavirus persistence.