Kaposi's sarcoma-associated herpesvirus (KSHV) has implicated Kaposi's sarcoma (KS), as well as primary effusion lymphomas (PELs) and multicentric Castleman's disease (MCD). KSHV belongs to the rhadinovirus or gamma-2 grouping of gamma herpesviruses. Lack of an efficient permissive lytic cell culture system for KSHV, has hampered the study of KSHV genes in the context of viral infection. Rhesus monkey rhadinovirus (RRV), originally isolated from rhesus macaques, is very closely related to KSHV and most of the eighty open reading frames (ORFs) of RRV share high homology with the corresponding ORFs of KSHV. Like KSHV, RRV has also been classified as a rhadinovirus. RRV is useful to the study of KSHV pathogenesis because unlike KSHV, RRV has a permissive lytic system and the virus can be grown to very high titers. In addition, the availability of an in vivo animal model, the rhesus macaque, suggests that RRV can serve as an invaluable animal model system for the study of KSHV. Our lab has recently characterized the lytic transcription program of RRV, which is very similar to the transcription program of KSHV. In this applicant application we propose to construct a Bacterial Artificial Chromosome (BAC) encoding the entire RRV genome using a self-recombining Cre-Lox strategy previously used to create the pseudorabies virus BAC. The advantage of generating a RRV-BAC virus is the ease with which we can generate recombinant viruses to analyze the function of any viral gene. Deletions, mutations and substitutions of a particular RRV gene will greatly enhance our knowledge on the function of that particular gene and its contribution to the pathogenesis of the virus. Thus, using the RRV-BAC system we will be able to generate any number of recombinant viruses that will enable us to examine the functions of specific viral genes in vitro as well as in vivo. Such an animal model system would help us understand the function of various genes in both the RRV and KSHV viral lifecycle. In addition, it would also help us shed light on the lifecycle and pathogenesis of the gamma herpesvirus family, in general. ? ?
| DeWire, Scott M; Damania, Blossom (2005) The latency-associated nuclear antigen of rhesus monkey rhadinovirus inhibits viral replication through repression of Orf50/Rta transcriptional activation. J Virol 79:3127-38 |
| Dittmer, Dirk P; Gonzalez, Carlos M; Vahrson, Wolfgang et al. (2005) Whole-genome transcription profiling of rhesus monkey rhadinovirus. J Virol 79:8637-50 |
