title: Multiple proviral integration events after virological synapse-mediated HIV-1 spread.
abstract: HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection. We found that HIV-1 cell-to-cell spread resulted in nuclear import of multiple proviruses into target cells as seen by fluorescence in-situ hybridization. Proviral integration into the target cell genome was significantly higher than that seen in a cell-free infection system, and consequent de novo viral DNA and RNA production in the target cell detected by quantitative PCR increased over time. Our data show efficient proviral integration across VS, implying the probability of multiple integration events in target cells that drive productive T cell infection.
authors.affiliation: The Sir William Dunn School of Pathology, The University of Oxford, South Parks Road, Oxford OX13RE, UK. rebecca.moore@path.ox.ac.uk
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Russell
authors.forename: Nicola
authors.initials: N
authors.lastname: Martin
authors.forename: Ivonne
authors.initials: I
authors.lastname: Mitar
authors.forename: Emma
authors.initials: E
authors.lastname: Jones
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Sattentau
mesh_terms: D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008856:Microscopy, Fluorescence; D011533:Proviruses / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000821:virology*; D016662:Virus Integration; D053586:Virus Internalization; D057074:Virus Release; D014779:Virus Replication