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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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 - Jan 1 1990

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Monocytes
HIV
T-Lymphocytes
Infection
Macrophages
HIV Envelope Protein gp120
Virus Diseases
Virion
HIV Infections
Deltaretrovirus Infections
Viruses
Virus Release
Cell Line
Virus Internalization
Tropism
recombinant soluble CD4
Giant Cells
Cell Culture Techniques
Lymph Nodes
Lung

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Gomatos, P. J., Stomatos, N. M., Gendelman, H. E., Fowler, A., Hoover, D. L., Kalter, D. 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.

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

In: Journal of Immunology, Vol. 144, No. 11, 01.01.1990, p. 4183-4188.

Research output: Contribution to journalArticle

Gomatos, PJ, Stomatos, NM, Gendelman, HE, Fowler, A, Hoover, DL, Kalter, DC, Burke, DS, Tramont, EC & Meltzer, MS 1990, 'Relative inefficiency of soluble recombinant CD4 for inhibition of infection by monocyte-tropic HIV in monocytes and T cells', Journal of Immunology, vol. 144, no. 11, pp. 4183-4188.
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. / Relative inefficiency of soluble recombinant CD4 for inhibition of infection by monocyte-tropic HIV in monocytes and T cells. In: Journal of Immunology. 1990 ; Vol. 144, No. 11. pp. 4183-4188.
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