HHV-8 is a human herpesvirus, also known as KSHV, which has been shown to encode a homologue of the human cytokine, IL-6. Human IL-6 (huIL6), levels of which are elevated in HIV infection, is known to be a potent enhancer of HIV replication in monocytes, but not T-cells. In their preliminary studies, the applicants have also seen that vIL6 is capable of inducing latent HIV-l in the monocytic cell line, Ul. The first specific aim is to extend and confirm this observation by examining the effects of vIL6 on HIV infection in primary monocytes and T-cells, as well as in cell lines containing HIV-1, and its potential to interact with inflammatory cytokines.
The second aim i s to investigate the signaling pathways used by huIL6 and vIL6 in monocytes and T-cells by studying components of the known huIL6 signaling pathways, specifically, the JAK/STAT and MAPK/NF- IL6 pathways, as well as cellular inhibitors of huIL6 such as the SSIs and PIAS3. These studies will provide information about the potential role of HHV-8 in HIV disease, as well as the role of cytokines in HIV replication and transcription in monocytes and T-cells.
|Breen, E C; Gage, J R; Guo, B et al. (2001) Viral interleukin 6 stimulates human peripheral blood B cells that are unresponsive to human interleukin 6. Cell Immunol 212:118-25|
|Gage, J R; Breen, E C; Echeverri, A et al. (1999) Human herpesvirus 8-encoded interleukin 6 activates HIV-1 in the U1 monocytic cell line. AIDS 13:1851-5|