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HIV-1 replication in dendritic cells occurs through a tetraspanin-containing compartment enriched in AP-3

Garcia, Eduardo, Nikolic, Damjan S. and Piguet, Vincent 2008. HIV-1 replication in dendritic cells occurs through a tetraspanin-containing compartment enriched in AP-3. Traffic 9 (2) , pp. 200-214. 10.1111/j.1600-0854.2007.00678.x

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Abstract

Dendritic cells (DC) are crucial components of the early events of HIV infection. Dendritic cells capture and internalize HIV at mucosal surfaces and efficiently transfer the virus to CD4+ T cells in trans through infectious synapses (trans-infection pathway). Alternatively, HIV-1 replicates in DC (R5-HIV-1) (cis-infection pathway). Here, we analyzed HIV trafficking in DC during the trans-infection pathway as well as the cis-infection pathway. Confocal immunofluorescence microscopy demonstrated that after capture by DC, R5-HIV-1 and HIV-1 pseudotyped with vesicular stomatitis virus protein G colocalized in a viral compartment enriched in tetraspanins including CD81, CD82 and CD9, although at different levels, indicating a role of the viral envelope in targeting to the tetraspanin-rich compartment. Replication of R5-HIV-1 in DC (cis-infection pathway) also led to the accumulation, in an envelope-independent manner, of mature viral particles in a tetraspanin-rich compartment. A fraction of the HIV-1-containing compartments appeared directly accessible from the cell surface. In sharp contrast with the trans-infection pathway, the δ-subunit of the adaptor protein 3 (AP-3) complex was enriched on the HIV-1-containing compartment during R5-HIV-1 replication in DC (cis-infection pathway). Downregulation of AP-3 δ-adaptin reduced significantly viral particle release from HIV-1-infected DC. Together, these studies demonstrate a role for AP-3 in HIV replication in a tetraspanin-rich compartment in DC and contribute to the elucidation of the trafficking pathways required for DC–T cell transfer of HIV-1 infection, a critical step during the early events of HIV infection.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: AP-3; dendritic cells; HIV-1; infectious synapse; tetraspanin; virological synapse; virus assembly
Publisher: Wiley-Blackwell
ISSN: 1398-9219
Last Modified: 04 Jun 2017 05:06
URI: http://orca.cf.ac.uk/id/eprint/48545

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