title: Distinct requirements for HIV-cell fusion and HIV-mediated cell-cell fusion.
abstract: Whether HIV-1 enters cells by fusing with the plasma membrane or with endosomes is a subject of active debate. The ability of HIV-1 to mediate fusion between adjacent cells, a process referred to as "fusion-from-without" (FFWO), shows that this virus can fuse with the plasma membrane. To compare FFWO occurring at the cell surface with HIV-cell fusion through a conventional entry route, we designed an experimental approach that enabled the measurements of both processes in the same sample. The following key differences were observed. First, a very small fraction of viruses fusing with target cells participated in FFWO. Second, whereas HIV-1 fusion with adherent cells was insensitive to actin inhibitors, post-CD4/coreceptor binding steps during FFWO were abrogated. A partial dependence of HIV-cell fusion on actin remodeling was observed in CD4(+) T cells, but this effect appeared to be due to the actin dependence of virus uptake. Third, deletion of the cytoplasmic tail of HIV-1 gp41 dramatically enhanced the ability of the virus to promote FFWO, while having a modest effect on virus-cell fusion. Distinct efficiencies and actin dependences of FFWO versus HIV-cell fusion are consistent with the notion that, except for a minor fraction of particles that mediate fusion between the plasma membranes of adjacent cells, HIV-1 enters through an endocytic pathway. We surmise, however, that cell-cell contacts enabling HIV-1 fusion with the plasma membrane could be favored at the sites of high density of target cells, such as lymph nodes.
authors.affiliation: From the Division of Pediatric Infectious Diseases, Emory University Children's Center, Atlanta and.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kondo
authors.affiliation: From the Division of Pediatric Infectious Diseases, Emory University Children's Center, Atlanta and.
authors.forename: Mariana
authors.initials: M
authors.lastname: Marin
authors.affiliation: From the Division of Pediatric Infectious Diseases, Emory University Children's Center, Atlanta and.
authors.forename: Jeong Hwa
authors.initials: JH
authors.lastname: Kim
authors.affiliation: From the Division of Pediatric Infectious Diseases, Emory University Children's Center, Atlanta and.
authors.forename: Tanay M
authors.initials: TM
authors.lastname: Desai
authors.affiliation: From the Division of Pediatric Infectious Diseases, Emory University Children's Center, Atlanta and Children's Healthcare of Atlanta, Atlanta, Georgia 30322 gmeliki@emory.edu.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Melikyan
mesh_terms: D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism / Q000821:virology; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics*; D011992:Endosomes / Q000378:metabolism / Q000821:virology; D057809:HEK293 Cells; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008561:Membrane Fusion / Q000235:genetics*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015700:HIV Envelope Protein gp41; D014760:Viral Fusion Proteins
keywords: Cytoskeleton; Endocytosis; Fluorescence; Membrane Fusion; Plasma Membrane