REGULATION OF INTERFERON-ALPHA-INDUCIBLE CELLULAR GENES IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED MONOCYTES

Cellular mechanisms that control susceptibility to opportunistic infec tion in human immunodeficiency virus (HIV)-infected individuals remain poorly understood. HIV may induce certain cellular genes that restric t HIV replication and protect cells against other superinfecting viral pathogens. Indeed, HIV-infected monocytes resist infection by vesicul ar stomatitis virus (VSV). HIV-induced VSV interference in monocytes i ncreases with time after HIV infection. Such interference was evident 6 h after HIV infection and reached maximal levels at 14 days. Monocyt otropic but not T cell-tropic HIV strains elicited these effects, sign aling a requirement for viral entry and/or replication. Viral interfer ence was independent of interferon (IFN) and was unaffected by additio n of neutralizing IFN-alpha and -beta antibodies. The well-described I FN-alpha-inducible antiviral pathways were examined to determine their relationship to the cellular mechanism(s) underlying VSV interference . HIV and IFN-alpha both induced the expression of 2-5A synthetase and Mx gene. In contrast, the guanylate-binding protein (GBP), 6-16, and 9-27 cellular genes were up-regulated by IFN-alpha but not HIV. MxA wa s detected in HIV-infected monocytes but not in uninfected monocytes. The association between Mx expression and resistance to VSV, coupled w ith previously described anti-VSV activities by human MxA, suggested t hat Mr may be an effector molecule for the HIV-induced anti-VSV activi ties. These results, taken together, suggest that HIV can induce antiv iral cellular gene expression, independent of IFN.