title: HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral therapy.
abstract: HIV spreads more efficiently in vitro when infected cells directly contact uninfected cells to form virological synapses. A hallmark of virological synapses is that viruses can be transmitted at a higher multiplicity of infection (MOI) that, in vitro, results in a higher number of proviruses. Whether HIV also spreads by cell-cell contact in vivo is a matter of debate. Here we discuss recent data that suggest that contact-mediated transmission largely manifests itself in vivo as CD4+ T cell depletion. The assault of a cell by a large number of incoming particles is likely to be efficiently sensed by the innate cellular surveillance to trigger cell death. The large number of particles transferred across virological synapses has also been implicated in reduced efficacy of antiretroviral therapies. Thus, antiretroviral therapies must remain effective against the high MOI observed during cell-to-cell transmission to inhibit both viral replication and the pathogenesis associated with HIV infection.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA; Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: luis.agosto.82@gmail.com.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Agosto
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Pradeep D
authors.initials: PD
authors.lastname: Uchil
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA. Electronic address: walther.mothes@yale.edu.
authors.forename: Walther
authors.initials: W
authors.lastname: Mothes
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure / Q000821:virology*; D002460:Cell Line; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D011533:Proviruses; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase
keywords: antiretroviral therapy; cell-to-cell transmission; human immunodeficiency virus; virological synapse