R5 HIV env and vesicular stomatitis virus G protein cooperate to mediate fusion to naive CD4+ T Cells.
Naïve CD4(4) T cells are resistant to both HIV R5 env and vesicular stomatitis virus G protein (VSV-G)-mediated fusion. However, viral particles carrying both HIV R5 env and VSV-G infect naïve cells by an unexplained mechanism. We show that VSV-G-pseudotyped virus cannot fuse to unstimulated cells because the viral particles cannot be endocytosed. However, virions carrying both HIV R5 env and VSV-G can fuse because CD4 binding allows viral uptake. Our findings reveal a unique mechanism by which R5 HIV env and VSV-G cooperate to allow entry to naïve CD4(+) T cells, providing a tool to target naïve CD4(+) T cells with R5 HIV to study HIV coreceptor signaling and latency.
Pace
Matthew J
MJ
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Room 272, John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104, USA.
Agosto
Luis
L
O'Doherty
Una
U
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D014759:Viral Envelope Proteins; D054299:env Gene Products, Human Immunodeficiency Virus