Toward a surrogate model for hepatitis C virus: An infectious molecular clone of the GB virus-B hepatitis agent

GB virus-B (GBV-B) is a member of the Flaviviridae family of viruses. This RNA virus infects tamarins, but its natural host is not known. GBV-B has sp ecial interest because it is the virus that is most closely related to hepa titis C virus (HCV), an important human pathogen. In the present study, we identified a previously unrecognized sequence at the 3' end of the GBV-B ge nome. This new 3' terminal sequence can farm several predicted stem-loop st ructures as is typical for other members of the Flaviviridae family. We con structed molecular clones and showed that the new 3' UTR sequence was criti cal for in vivo infectivity. After intrahepatic transfection of two tamarin s with RNA transcripts of the full-length GBV-B clone, we detected high vir al titers from Week 1 postinoculation with peak titers of similar to 10(8) genome equivalents/ml. The viremic pattern of GBV-B infection in the transf ected animals was the same as in animals inoculated intravenously with the virus pool used as the cloning source. The sequence of the recombinant viru s was recovered from one of the tamarins and shown to be identical to that of the infectious clone. The development of severe hepatitis in both tamari ns infected with the recombinant GBV-B virus provides formal proof that GBV -B is a true hepatitis virus. (C) 1999 Academic Press.