Macrophage-Tropic Strains of Human Immunodeficiency Virus Type 1 Utilize the CD4 Receptor

Ronald Collman, Brian Godfrey, Joann Cutilli, Audrey Rhodes, Nassef F. Hassan, Ray Sweet, Steven D. Douglas, Harvey Friedman, Neal Nathanson, Francisco Gonzalez-Scarano

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

To characterize the role of CD4 in human immunodeficiency virus type 1 (HIV-1) infection of macrophages, we examined the expression of CD4 by primary human monocyte-derived macrophages and studied the effect of recombinant soluble CD4 and anti-CD4 monoclonal antibodies on HIV-1 infection of these cells. Immunofluorescence and Western blot (immunoblot) studies demonstrated that both monocytes and macrophages display low levels of surface CD4, which is identical in mobility to CD4 in lymphocytes. Recombinant soluble CD4 and the anti-CD4 monoclonal antibody Leu3a blocked infection of macrophages by three different macrophage-tropic HIV isolates, and the cytopathic effects of HIV-1 infection were similarly prevented. Dose-response experiments using a prototype isolate which replicates in both macrophages and T lymphocytes showed that recombinant soluble CD4 inhibited infection of macrophages more efficiently than in lymphocytes. These results indicate that CD4 is the dominant entry pathway for HIV-1 infection of macrophages. In addition, recombinant soluble CD4 effectively blocks HIV-1 infection by a variety of macrophage-tropic strains and thus has the potential for therapeutic use in macrophage-dependent pathogenesis in HIV disease.

Original languageEnglish (US)
Pages (from-to)4468-4476
Number of pages9
JournalJournal of Virology
Volume64
Issue number9
StatePublished - 1990
Externally publishedYes

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CD4 Antigens
Human immunodeficiency virus 1
HIV-1
tropics
macrophages
Macrophages
receptors
Virus Diseases
infection
monocytes
monoclonal antibodies
lymphocytes
Monoclonal Antibodies
HIV
Lymphocytes
cytopathogenicity
Therapeutic Uses
Infection
prototypes
fluorescent antibody technique

ASJC Scopus subject areas

  • Immunology

Cite this

Collman, R., Godfrey, B., Cutilli, J., Rhodes, A., Hassan, N. F., Sweet, R., ... Gonzalez-Scarano, F. (1990). Macrophage-Tropic Strains of Human Immunodeficiency Virus Type 1 Utilize the CD4 Receptor. Journal of Virology, 64(9), 4468-4476.

Macrophage-Tropic Strains of Human Immunodeficiency Virus Type 1 Utilize the CD4 Receptor. / Collman, Ronald; Godfrey, Brian; Cutilli, Joann; Rhodes, Audrey; Hassan, Nassef F.; Sweet, Ray; Douglas, Steven D.; Friedman, Harvey; Nathanson, Neal; Gonzalez-Scarano, Francisco.

In: Journal of Virology, Vol. 64, No. 9, 1990, p. 4468-4476.

Research output: Contribution to journalArticle

Collman, R, Godfrey, B, Cutilli, J, Rhodes, A, Hassan, NF, Sweet, R, Douglas, SD, Friedman, H, Nathanson, N & Gonzalez-Scarano, F 1990, 'Macrophage-Tropic Strains of Human Immunodeficiency Virus Type 1 Utilize the CD4 Receptor', Journal of Virology, vol. 64, no. 9, pp. 4468-4476.
Collman R, Godfrey B, Cutilli J, Rhodes A, Hassan NF, Sweet R et al. Macrophage-Tropic Strains of Human Immunodeficiency Virus Type 1 Utilize the CD4 Receptor. Journal of Virology. 1990;64(9):4468-4476.
Collman, Ronald ; Godfrey, Brian ; Cutilli, Joann ; Rhodes, Audrey ; Hassan, Nassef F. ; Sweet, Ray ; Douglas, Steven D. ; Friedman, Harvey ; Nathanson, Neal ; Gonzalez-Scarano, Francisco. / Macrophage-Tropic Strains of Human Immunodeficiency Virus Type 1 Utilize the CD4 Receptor. In: Journal of Virology. 1990 ; Vol. 64, No. 9. pp. 4468-4476.
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