SUBCELLULAR-DISTRIBUTION OF LARGE AND SMALL HEPATITIS-DELTA ANTIGEN IN HEPATOCYTES OF HEPATITIS-DELTA VIRUS SUPERINFECTED WOODCHUCKS

Hepatitis delta virus (HDV) encodes only a single protein, the hepatit is delta antigen (HDAg), which is expressed as two molecular forms (la rge and small) with different functions in viral replication, Compared with small antigen, large antigen has a 19 residue carboxyl terminal extension, Antibodies that recognize a large antigen-specific epitope within this carboxyl extension, or an epitope shared by both large and small antigens (total antigen), were used in immunohistochemical stud ies of liver sections from superinfected woodchuck carriers of woodchu ck hepatitis virus. There were no differences in the subcellular distr ibutions of large and total antigens, with both generally present only in nuclei of hepatocytes. Rare cells demonstrated cytoplasmic stainin g, Complete or partial granular nucleoplasmic staining with stained nu cleoli was the most common pattern observed. Within 31 days of infecti on, 0.1% to 19% (mean = 7.4%) of all hepatocytes contained antigen. Th e proportion of these nuclei containing large antigen ranged from 0 to 100% (mean, 39%), and increased during the first month of infection, The number of antigen-positive nuclei and the proportion staining for large antigen were reduced with progression to chronicity, correlating with reductions in the level of viremia. Thus, the large hepatitis de lta antigen shares a common subcellular distribution with small antige n and is found in an increasing proportion of the nuclei of infected c ells during the course of acute infection.