Regulation of interferon-α-inducible cellular genes in human immunodeficiency virus-infected monocytes

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Abstract
Cellular mechanisms that control susceptibility to opportunistic infection in human immunodeficiency virus (HIV)-infected individuals remain poorly understood. HIV may induce certain cellular genes that restrict HIV replication and protect cells against other superinfecting viral pathogens. Indeed, HIV-infected monocytes resist infection by vesicular stomatitis virus (VSV). HIV-induced VSV interference in monocytes increases with time after HIV infection. Such interference was evident 6 h after HIV infection and reached maximal levels at 14 days. Monocytotropic but not T cell-tropic HIV strains elicited these effects, signaling a requirement for viral entry and/or replication. Viral interference was independent of interferon (IFN) and was unaffected by addition of neutralizing IFN-α and -β antibodies. The well-described IFN-α-inducible antiviral pathways were examined to determine their relationship to the cellular mechanism(s) underlying VSV interference. HIV and IFN-α 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-α but not HIV. MxA was detected in HIV-infected monocytes but not in uninfected monocytes. The association between Mx expression and resistance to VSV, coupled with previously described anti-VSV activities by human MxA, suggested that Mx may be an effector molecule for the HIV-induced anti-VSV activities. These results, taken together, suggest that HIV can induce antiviral cellular gene expression, independent of IFN. J. Lcukoc. Biol. 55: 299–309; 1994.

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