title: Cell-to-cell transmission can overcome multiple donor and target cell barriers imposed on cell-free HIV.
abstract: Virus transmission can occur either by a cell-free mode through the extracellular space or by cell-to-cell transmission involving direct cell-to-cell contact. The factors that determine whether a virus spreads by either pathway are poorly understood. Here, we assessed the relative contribution of cell-free and cell-to-cell transmission to the spreading of the human immunodeficiency virus (HIV). We demonstrate that HIV can spread by a cell-free pathway if all the steps of the viral replication cycle are efficiently supported in highly permissive cells. However, when the cell-free path was systematically hindered at various steps, HIV transmission became contact-dependent. Cell-to-cell transmission overcame barriers introduced in the donor cell at the level of gene expression and surface retention by the restriction factor tetherin. Moreover, neutralizing antibodies that efficiently inhibit cell-free HIV were less effective against cell-to-cell transmitted virus. HIV cell-to-cell transmission also efficiently infected target T cells that were relatively poorly susceptible to cell-free HIV. Importantly, we demonstrate that the donor and target cell types influence critically the extent by which cell-to-cell transmission can overcome each barrier. Mechanistically, cell-to-cell transmission promoted HIV spread to more cells and infected target cells with a higher proviral content than observed for cell-free virus. Our data demonstrate that the frequently observed contact-dependent spread of HIV is the result of specific features in donor and target cell types, thus offering an explanation for conflicting reports on the extent of cell-to-cell transmission of HIV.
authors: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
authors: Peng
authors: P
authors: Zhong
authors: Luis M
authors: LM
authors: Agosto
authors: Anna
authors: A
authors: Ilinskaya
authors: Batsukh
authors: B
authors: Dorjbal
authors: Rosaline
authors: R
authors: Truong
authors: David
authors: D
authors: Derse
authors: Pradeep D
authors: PD
authors: Uchil
authors: Gisela
authors: G
authors: Heidecker
authors: Walther
authors: W
authors: Mothes
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006678:HIV / Q000472:pathogenicity* / Q000502:physiology; D015658:HIV Infections / Q000276:immunology / Q000635:transmission* / Q000821:virology; D006801:Humans; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000821:virology; D053586:Virus Internalization
chemical_list: D057134:Antibodies, Neutralizing