Complete nucleotide sequence and viral envelope protein expression of a hepatitis B virus DNA derived from a...

An HBV strain isolated from a patient lacking conventional serological markers of HBV infection was characterized. The complete nucleotide sequence was determined following PCR amplification. Only 22 nucleotide substitutions were found relative to the reported sequence of the ayw subtype. Five of these point mutations in the preS/S and preC/C genes led to amino acid substitutions and, with one exception, were located in regions coding for antigenic determinants of viral envelope or capsid proteins. Eight amino acid substitutions were located in terminal protein and the spacer domain of the polymerase gene product. Despite these amino acid changes, transient expression of the preS2 and S envelope proteins in eucaryotic cells yielded viral proteins detectable in the culture medium with polyclonal and monoclonal anti-preS2 and -S antibodies. These data conclusively demonstrate persistent infection by HBV in subjects without HBV serological markers. The absence of conventional HBV serological markers is probably due to several factors: a low level of viral replication, some genetic modifications, as well as an abnormal immune response to the virus.