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HIV envelope induces a cascade of cell signals in non- proliferating target cells that favor virus replication

  1. Author:
    Cicala, C.
    Arthos, J.
    Selig, S. M.
    Dennis, G.
    Hosack, D. A.
    Van Ryk, D.
    Spangler, M. L.
    Steenbeke, T. D.
    Khazanie, P.
    Gupta, N.
    Yang, J.
    Daucher, M.
    Lempicki, R. A.
    Fauci, A. S.

  2. Author Address

    10 Ctr Dr,MSC 1876,Bldg 10,Room 11B13, Bethesda, MD 20892 USA NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA NIAID, Lab Immunopathogenesis & Bioinformat, NIH, Frederick, MD 21702 USA Cicala C 10 Ctr Dr,MSC 1876,Bldg 10,Room 11B13, Bethesda, MD 20892 USA
    1. Year: 2002
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 99
    2. 14
    3. Pages: 9380-9385
  4. Type of Article: Article
  1. Abstract:

    Certain HIV-encoded proteins modify host-cell gene expression in a manner that facilitates viral replication. These activities may contribute to low-level viral replication in nonproliferating cells. Through the use of oligonucleotide microarrays and high-throughput Western blotting we demonstrate that one of these proteins, gp120, induces the expression of cytokines, chemokines, kinases, and transcription factors associated with antigen-specific T cell activation in the absence of cellular proliferation. Examination of transcriptional changes induced by gp120 in freshly isolated peripheral blood mononuclear cells and monocyte-derived macrophages reveals a broad and complex transcriptional program conducive to productive infection with HIV. Observations include the induction of nuclear factor of activated T cells, components of the RNA polymerase 11 complex including TFII D, proteins localized to the plasma membrane, including several syntaxins, and members of the Rho protein family, including Cdc 42. These observations provide evidence that envelope-mediated signaling contributes to the productive infection of HIV in suboptimally activated T cells.

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