Potential role for CD63 in CCR5-mediated human immunodeficiency virus type 1 infection of macrophages.
Macrophages and CD4(+) lymphocytes are the principal target cells for human immunodeficiency virus type 1 (HIV-1) infection, but the molecular details of infection may differ between these cell types. During studies to identify cellular molecules that could be involved in macrophage infection, we observed inhibition of HIV-1 infection of macrophages by monoclonal antibody (MAb) to the tetraspan transmembrane glycoprotein CD63. Pretreatment of primary macrophages with anti-CD63 MAb, but not MAbs to other macrophage cell surface tetraspanins (CD9, CD81, and CD82), was shown to inhibit infection by several R5 and dualtropic strains, but not by X4 isolates. The block to productive infection was postfusion, as assessed by macrophage cell-cell fusion assays, but was prior to reverse transcription, as determined by quantitative PCR assay for new viral DNA formation. The inhibitory effects of anti-CD63 in primary macrophages could not be explained by changes in the levels of CD4, CCR5, or beta-chemokines. Infections of peripheral blood lymphocytes and certain cell lines were unaffected by treatment with anti-CD63, suggesting that the role of CD63 in HIV-1 infection may be specific for macrophages.
von Lindern
Jana J
JJ
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Rojo
Daniel
D
Grovit-Ferbas
Kathie
K
Yeramian
Christine
C
Deng
Cheng
C
Herbein
Georges
G
Ferguson
Monique R
MR
Pappas
Todd C
TC
Decker
Julie M
JM
Singh
Anjali
A
Collman
Ronald G
RG
O'Brien
William A
WA
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D008264:Macrophages / Q000821:virology*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000378:metabolism*; D060149:Tetraspanin 30
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015704:CD4 Antigens; C554586:CD63 protein, human; D004279:DNA, Viral; D010980:Platelet Membrane Glycoproteins; D019713:Receptors, CCR5; D060149:Tetraspanin 30