Attenuation of HIV-1 replication in macrophages by cannabinoid receptor 2 agonists.

ABSTRACT: Infiltrating monocytes and macrophages play a crucial role in the progression of HIV-1 infection in the CNS. Previous studies showed that activation of the CB? can attenuate inflammatory responses and affect HIV-1 infectivity in T cells and microglia. Here, we report that CB? agonists can also act as immunomodulators on HIV-1-infected macrophages. First, our findings indicated the presence of elevated levels of CB? expression on monocytes/macrophages in perivascular cuffs of postmortem HIV-1 encephalitic cases. In vitro analysis by FACS of primary human monocytes revealed a step-wise increase in CB? surface expression in monocytes, MDMs, and HIV-1-infected MDMs. We next tested the notion that up-regulation of CB? may allow for the use of synthetic CB? agonist to limit HIV-1 infection. Two commercially available CB? agonists, JWH133 and GP1a, and a resorcinol-based CB? agonist, O-1966, were evaluated. Results from measurements of HIV-1 RT activity in the culture media of 7 day-infected cells showed a significant decrease in RT activity when the CB? agonist was present. Furthermore, CB? activation also partially inhibited the expression of HIV-1 pol. CB? agonists did not modulate surface expression of CXCR4 or CCR5 detected by FACS. We speculate that these findings indicate that prevention of viral entry is not a central mechanism for CB?-mediated suppression in viral replication. However, CB? may affect the HIV-1 replication machinery. Results from a single-round infection with the pseudotyped virus revealed a marked decrease in HIV-1 LTR activation by the CB? ligands. Together, these results indicate that CB? may offer a means to limit HIV-1 infection in macrophages.

SUBMITTER: Ramirez SH 

PROVIDER: S-EPMC3629438 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature