High level of coreceptor-independent HIV transfer induced by contacts between primary CD4 T cells.
Cell-to-cell virus transmission is one of the most efficient mechanisms of human immunodeficiency virus (HIV) spread, requires CD4 and coreceptor expression in target cells, and may also lead to syncytium formation and cell death. Here, we show that in addition to this classical coreceptor-mediated transmission, the contact between HIV-producing cells and primary CD4 T cells lacking the appropriate coreceptor induced the uptake of HIV particles by target cells in the absence of membrane fusion or productive HIV replication. HIV uptake by CD4 T cells required cellular contacts mediated by the binding of gp120 to CD4 and intact actin cytoskeleton. HIV antigens taken up by CD4 T cells were rapidly endocytosed to trypsin-resistant compartments inducing a partial disappearance of CD4 molecules from the cell surface. Once the cellular contact was stopped, captured HIV were released as infectious particles. Electron microscopy revealed that HIV particles attached to the surface of target cells and accumulated in large (0.5-1.0 microm) intracellular vesicles containing 1-14 virions, without any evidence for massive clathrin-mediated HIV endocytosis. The capture of HIV particles into trypsin-resistant compartments required the availability of the gp120 binding site of CD4 but was independent of the intracytoplasmic tail of CD4. In conclusion, we describe a novel mechanism of HIV transmission, activated by the contact of infected and uninfected primary CD4 T cells, by which HIV could exploit CD4 T cells lacking the appropriate coreceptor as an itinerant virus reservoir.
Blanco
Julià
J
Retrovirology Laboratory, Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. jblanco@ns.hugtip.scs.es
Bosch
Berta
B
Fernández-Figueras
María Teresa
MT
Barretina
Jordi
J
Clotet
Bonaventura
B
Esté
José A
JA
D000199:Actins / Q000378:metabolism; D001665:Binding Sites; D015704:CD4 Antigens / Q000096:biosynthesis / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004705:Endocytosis; D005434:Flow Cytometry; D006678:HIV / Q000378:metabolism*; D016655:HIV Core Protein p24 / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000635:transmission; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008854:Microscopy, Electron; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology
D000199:Actins; D015704:CD4 Antigens; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D014357:Trypsin