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A potent anti-HIV immunotoxin blocks spreading infection by primary HIV type 1 isolates in multiple cell types

  1. Author:
    Lueders, K. K.
    De Rosa, S. C.
    Valentin, A.
    Pavlakis, G. N.
    Roederer, M.
    Hamer, D. H.

  2. Author Address

    Hamer, DH, NCI, Biochem Lab, NIH, Bld 37,Rm 6002,9000 Rockville Pike, Bethesda, MD 20892 USA NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NCI, Human Retrovirus Sect, Basic Res Lab, Frederick, MD 21702 USA.
    1. Year: 2004
  2. Journal: Aids Research and Human Retroviruses
    1. 20
    2. 2
    3. Pages: 145-150
  4. Type of Article: Article
  1. Abstract:

    Although several immunotoxins that selectively kill HIV-1-infected cells have been described, their clinical utility is limited by low potency against spreading viral infection. We show here that changing the carboxyterminal sequence of an anti-HIV-1 envelope immunotoxin to the consensus endoplasmic reticulum retention sequence KDEL substantially improves its ability to block infection of peripheral blood mononuclear cells by primary HIV-1 isolates without increasing nonspecific toxicity. Polychromatic flow cytometry of peripheral blood mononuclear cells (PBMC) infected with an HIV-1-GFP reporter virus demonstrated that the improved immunotoxin is active against a variety of primary cell types including memory T cells, NK-T cells, and monocyte/macrophages. The subnanomolar potency of this agent suggests that it could be clinically useful either as an adjuvant to highly active antiretroviral therapy (HAART) in drug-resistant patients or to reduce the reservoir of latently infected cells that is implicated in HIV-1 persistence

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