This project studies human viruses and their life cycle at the molecular level, correlates this with pathogenesis, and attempts to develop approaches to antiviral therapy. Viruses include human immunodeficiency virus type 1 (HIV-1), human herpesviruses 7 (HHV-7) and HHV-8 (Kaposi's sarcoma-related human herpesvirus). Progress has been made in several areas: 1) phosphorothioate oligonucleotides antisense to several regions in the HIV-1 long terminal repeat, including those around the polyadenylation signal, have been found to be effective against HIV-1 replication in tissue culture; 2) intracellular expression of antibodies to reverse transcriptase has been shown to inhibit HIV-1 replication prior to the establishment of integrated provirus, and is effective against different viral strains including primary isolates; 3) HIV-1 integrase has been shown to be necessary for sustained viral replication , although limited replication is seen with primary monocyte-macrophages. The integrase also seems to play a role, which may be indirect, in virion assembly and release; 4) a messenger ribonucleic acid-polymerase chain reaction differential display technique has been established and candidate probes for genes expressed in tumorigenic, but not nontumorigenic, sublines of a Kaposi's sarcoma immortalized cell line have been obtained; 5) a gene which may be relevant to the neurologic disease induced by human T-cell leukemia/lymphotropic virus type I has been obtained by subtractive hybridization; and 6) envelope genes gH and gB of HHV-7, which may be responsible for inhibition of HIV replication by HHV-7, have been identified and characterized molecularly.
