Delayed clearance of HBV-DNA detected by PCR in the absence of viral replication.

Abstract

The polymerase chain reaction (PCR) was used to study the in vivo persistence and clearance of HBV-DNA in the serum of a monkey (Macaca mulatta) known to be naturally resistant to the HBV infection. Total infectious plasma, virus pellet, and viral DNA were inoculated into 3 different monkeys. Degradation of infectious particles and clearance of HBV-DNA were analyzed by detecting HBV-DNA sequences in serial dilutions of serum by dot blot hybridization and PCR. Semi-quantitation was carried out by comparison with minimal positive dilutions of known HBV-DNA. The presence of hepatitis B surface antigen (HB-sAg) and hepatitis B e antigen (HBeAg) in serum was also investigated. PCR assays were found positive in serial samples of the 3 monkeys, and passively transmitted viral DNA remained detectable for 3 months after inoculation. HBsAg and HBeAg were detectable for 3 weeks and 2 weeks, respectively, in a monkey inoculated with total infectious plasma. Semi-quantitation of HBV viremia showed that the amount of virus detected 1 day after injection was markedly decreased and persisted at a low level, showing a rapid and important sequestration of viral particles. Since replication can be excluded in these monkeys, the data show that HBV-DNA sequences can remain detectable at a low level in the serum for long periods. It is thus conceivable that PCR may also detect the HBV genome, eventually degraded in vivo, and a weakly positive result does not always mean ongoing viral replication.(ABSTRACT TRUNCATED AT 250 WORDS)