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

L. M. Baca, P. Genis, D. Kalvakolanu, G. Sen, M. S. Meltzer, A. Zhou, R. Silverman, H. E. Gendelman

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)299-309
Number of pages11
JournalJournal of Leukocyte Biology
Volume55
Issue number3
DOIs
StatePublished - Jan 1 1994

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Keywords

  • HIV-infected monocytes
  • INF-α-inducible genes
  • vesicular stomatitis virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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