Cell-to-cell transfer of HIV-1 via virological synapses leads to endosomal virion maturation that activates viral membrane fusion

Benjamin M. Dale, Gregory P. McNerney, Deanna L. Thompson, Wolfgang Hubner, Kevin De Los Reyes, Frank Chuang, Thomas R Huser, Benjamin K. Chen

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

HIV-1 can infect T cells by cell-free virus or by direct virion transfer between cells through cell contact-induced structures called virological synapses (VS). During VS-mediated infection, virions accumulate within target cell endosomes. We show that after crossing the VS, the transferred virus undergoes both maturation and viral membrane fusion. Following VS transfer, viral membrane fusion occurs with delayed kinetics and transferred virions display reduced sensitivity to patient antisera compared to mature, cell-free virus. Furthermore, particle fusion requires that the transferred virions undergo proteolytic maturation within acceptor cell endosomes, which occurs over several hours. Rapid, live cell confocal microscopy demonstrated that viral fusion can occur in compartments that have moved away from the VS. Thus, HIV particle maturation activates viral fusion in target CD4+ T cell endosomes following transfer across the VS and may represent a pathway by which HIV evades antibody neutralization.

Original languageEnglish (US)
Pages (from-to)551-562
Number of pages12
JournalCell Host and Microbe
Volume10
Issue number6
DOIs
StatePublished - Dec 15 2011

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

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