Human immunodeficiency virus-infected monocyte-derived macrophages express surface gp120 and fuse with CD4 lymphoid cells in vitro: a possible mechanism of T lymphocyte depletion in vivo.
Monocyte-derived macrophages (MDM) infected in vitro with a macrophage-tropic strain of human immunodeficiency virus (HIV) fused with uninfected, CD4-expressing T lymphoblastoid cells, but not with a subclone of these cells lacking surface CD4. Infected MDM also fused with uninfected autologous and heterologous MDM. Recombinant soluble CD4 protein (rsCD4) (10 micrograms/ml) and full-length recombinant glycosylated gp120 (20 micrograms/ml) each inhibited fusion by 94-99%; the inhibition was dose-dependent. The N-terminal portion of gp120 did not inhibit syncytium formation. Fusion was also inhibited by a monoclonal antibody to an epitope which binds gp120 (S3.5), but not by antibody to an epitope not involved in gp120 binding (OKT4). HIV-infected MDM specifically bound fluorescein-conjugated rsCD4, and virus could be visualized budding from the surface of these cells. HIV-infected MDM express viral gp120 on their surface and fuse with CD4-bearing cells in a fashion similar to lymphoid cells. Macrophages may contribute to CD4 lymphocyte depletion in vivo by this fusion mechanism.
Department of Medicine, San Francisco General Hospital/University of California 94110.
S M
SM
Crowe
J
J
Mills
T
T
Elbeik
J D
JD
Lifson
J
J
Kosek
J A
JA
Marshall
E G
EG
Engleman
M S
MS
McGrath
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology* / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002459:Cell Fusion / Q000276:immunology; D002469:Cell Separation; D004306:Dose-Response Relationship, Immunologic; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis* / Q000502:physiology; D015497:HIV-1; D006801:Humans; D066298:In Vitro Techniques; D016169:Lymphocyte Function-Associated Antigen-1 / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D008854:Microscopy, Electron; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D016169:Lymphocyte Function-Associated Antigen-1; D011994:Recombinant Proteins