Relative inefficiency of soluble recombinant CD4 for inhibition of infection by monocyte-tropic HIV in monocytes and T cells

P. J. Gomatos, N. M. Stomatos, H. E. Gendelman, A. Fowler, D. L. Hoover, D. C. Kalter, D. S. Burke, E. C. Tramont, M. S. Meltzer

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38 Scopus citations

Abstract

Macrophages are major viral reservoirs in the brain, lungs, and lymph nodes of HIV-infected patients. But not all HIV isolates infect macrophages. The molecular basis for this restrictive target cell tropism and the mechanisms by which HIV infects macrophages are not well understood: virus uptake by CD4-dependent and -independent pathways have both been proposed. Soluble rCD4 (sCD4) binds with high affinity to gp120, the envelope glycoprotein of HIV, and at relatively low concentrations (< 1 μg/ml) completely inhibits infection of many HIV strains in T cells or T cell lines. HTLV-IIIB infection of the H9 T cell line was completely inhibited by prior treatment of virus with 10 μg/ml sCD4: no P24 Ag or HIV-induced T cell syncytia were detected in cultures of H9 cells exposed to 1 x 104 TCID50 HTLV-IIIB in the presence of sCD4. Under identical conditions and at a 100-fold lower viral inoculum, 10 μg/ml sCD4 had little or no effect on infection of monocytes by any of six different HIV isolates by three different criteria: p24 Ag release, virus-induced cytopathic effects, and the frequency of infected cells that express HIV-specific mRNA. At 10- to 100-fold higher concentrations of sCD4, however, infection was completely inhibited. Monoclonal anti-CD4 also prevented infection of these same viral isolates in monocytes. The relative inefficiency of sCD4 for inhibition of HIV infection in monocytes was a property of the virion, not the target cell: HIV isolates that infect both monocytes and T cells required similarly high levels of sCD4 (100 to 200 μg/ml) for inhibition of infection. These data suggest that the gp120 of progeny HIV derived from macrophages interacts with sCD4 differently than that of virions derived from T cells. For both variants of HIV, however, the predominant mechanism of virus entry for infection is CD4-dependent.

Original languageEnglish (US)
Pages (from-to)4183-4188
Number of pages6
JournalJournal of Immunology
Volume144
Issue number11
StatePublished - 1990

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Gomatos, P. J., Stomatos, N. M., Gendelman, H. E., Fowler, A., Hoover, D. L., Kalter, D. C., Burke, D. S., Tramont, E. C., & Meltzer, M. S. (1990). Relative inefficiency of soluble recombinant CD4 for inhibition of infection by monocyte-tropic HIV in monocytes and T cells. Journal of Immunology, 144(11), 4183-4188.