9th Conference on Retroviruses and Opportunistic Infections Seattle, Washington - February 24 -February 28, 2002

Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 26
Von Lindern J, Grovit-Ferbas K, Yeramian C, Pappas TC, Deng C, Herbein G, Ferguson M, O'Brien WA; Univ. of Texas Med. Branch, Galveston

BACKGROUND: Macrophages are important target cells for HIV infection and contribute to pathogenesis by serving as a long-lived viral reservoir. Culture or cytokine activated macrophages are more susceptible to HIV infection, as compared with monocytes. Identification of cellular factors that are involved in efficient HIV macrophage infection (in addition to CD4 and chemokine receptors) may lead to novel antiretroviral therapies.

METHODS: A myeloid cell-specific monoclonal antibody (mAb) library (n=142) was screened for increased binding to 7-day cultured macrophages, as compared with fresh monocytes, and were assessed for inhibition of HIV infection. Levels of infection were monitored by quantitative PCR and by p24 ELISA. Quantitative QT6 cell-cell fusion assay was assessed with CD4/coreceptor transfection, with and without CD63 cotransfection, incubated with HIV Env-expressing QT6 cells. Quantitative FACS (QFACS) analysis was used to measure changes in receptor/coreceptor levels following CD63 transfection.

RESULTS: Pretreatment with anti-CD63 mAb was shown to inhibit infection of primary macrophages by both M-tropic (R5) and dual tropic (R5X4) strains of HIV-1. The block to productive infection occurred prior to reverse transcription, as determined with a quantitative PCR assay for new viral DNA formation. In addition, transfection of QT6 cells with CD63 caused an increase in cell-cell fusion mediated by CD4/CCR5. CD63 cotransfection was also associated with a 7-fold increase in CD4 antibody binding sites per cell by QFACS analysis, whether or not expression of CCR5 or CXCR4 was induced. CCR5 and CXCR4 levels were not affected by CD63 coexpression or by anti-CD63 treatment.

CONCLUSIONS: It is likely that CD63 is involved in HIV infection of macrophages, particularly at the level of virus entry (binding or post-binding fusion). A potential mechanism of action is the maintenance of CD4 expression by reduction of CD4 turnover in macrophages.

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Copyright © 2002 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.