Laboratory of Retroviral Biochemistry Researchgroup

One of the major research interests of the LRB is to study the biochemistry and enzymology of retroviral replication, with an emphasis on the function and features of the viral proteinase (PR). All replication competent retroviruses code for a PR. The function of the mature PR is critical for virion replication. The HIV-1 PR has proved to be an excellent target for antiretroviral therapy of AIDS, and various PR inhibitors are now in clinical use. However, there is a rapid selection of viral variants that are resistant to inhibitors of PR. Comparative studies of various PRs have revealed the common features of their specificity. These studies are expected to aid the rational design of broad-spectrum inhibitors effective against various retroviral proteinases, including the mutant HIV-1 enzymes appearing in drug resistance. Previously we have studied and characterized the PR of the following retrovirues: HIV-1, HIV-2, equine infectious anemia virus, human T-cell leukemia virus, bovine leukemia virus, avian myeloblastosis virus, and human foamy virus. Currently we are concentrating on the characterization of mutant HIV-1 and HTLV-1 proteinases, as well as on the characterization of murine leukemia virus and mouse mammary tumor virus proteinases. Besides the detailed characterization of various retroviral PRs, we are also involved in the efforts to prove the previously suggested early-phase function of the PR The specificity of the proteases of eleven retroviruses was studied using a series of oligopeptides having single amino acid substitutions in various positions of a naturally occurring cleavage site of HIV-1. The protease set included at least one member from each of the seven genera of the family Retroviridae.