Hepatitis delta virus (HDV) encodes only a single
protein, the
hepatitis delta antigen (
HDAg), which is expressed as two molecular forms (large 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 studies of liver sections from superinfected woodchuck carriers of woodchuck hepatitis virus. There were no differences in the subcellular distributions of large and total
antigens, with both generally present only in nuclei of hepatocytes. Rare cells demonstrated cytoplasmic staining. Complete or partial granular nucleoplasmic staining with stained nucleoli was the most common pattern observed. Within 31 days of
infection, 0.1% to 19% (mean = 7.4%) of all hepatocytes contained
antigen. The 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 delta antigen shares a common subcellular distribution with small
antigen and is found in an increasing proportion of the nuclei of infected cells during the course of acute
infection.