Abstract
We previously reported that CD8+ T cell-derived factors enhanced HIV long terminal repeat (LTR)-mediated gene expression and replication in monocytic cell lines. We now report that replication of NSI and SI primary isolates of HIV-1 in human macrophages were significantly enhanced by CD8+ T cell supernatants. The CD8-mediated enhancement of HIV replication was abrogated by pertussis toxin in a dose-dependent manner. The sensitivity to pertussis toxin suggests that the CD8+ T cell-derived enhancing factor is acting through a G protein-coupled signalling pathway. Enhanced HIV replication in macrophages was accompanied by increased levels of HIV-1 mRNA, suggesting that CD8 enhancement was mediated at the transcriptional level. Interestingly, the replication of HIV(Bal), which replicates to high levels in macrophages, was not significantly modulated by culture with CD8+ T cell supernatants. Although direct co-culture of activated CD8+ T cells with HIV(Ada)-infected macrophages did not modulate replication, separation of the CD8+ T cells from macrophages in transwell cultures resulted in significant enhancement of replication. The inability to detect a modulatory effect in direct co-cultures appeared to be due to non-specific lysis of infected macrophages. Thus, soluble factors produced by CD8+ T cells exert strong enhancing effects on HIV-1 replication in human macrophages.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.