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Trends Microbiol. 2015 May;23(5):289-95. doi: 10.1016/j.tim.2015.02.003. Epub 2015 Mar 9.

HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral therapy.

Author information

1
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.
2
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
3
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA. Electronic address: walther.mothes@yale.edu.

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.

KEYWORDS:

antiretroviral therapy; cell-to-cell transmission; human immunodeficiency virus; virological synapse

PMID:
25766144
PMCID:
PMC4417442
DOI:
10.1016/j.tim.2015.02.003
[Indexed for MEDLINE]
Free PMC Article

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