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

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 delta-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 delta-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.
AuthorsEduardo Garcia, Damjan S Nikolic, Vincent Piguet
JournalTraffic (Copenhagen, Denmark) (Traffic) Vol. 9 Issue 2 Pg. 200-14 (Feb 2008) ISSN: 1398-9219 [Print] Denmark
PMID18034776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • AP3D1 protein, human
  • Adaptor Protein Complex 3
  • Adaptor Protein Complex delta Subunits
  • Antigens, CD
  • Antigens, CD63
  • Antigens, CD81
  • Antigens, CD82
  • Antigens, CD9
  • CD63 protein, human
  • CD81 protein, human
  • CD82 protein, human
  • CD9 protein, human
  • HIV Antigens
  • HLA-DR Antigens
  • LAMP1 protein, human
  • Lysosome-Associated Membrane Glycoproteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Platelet Membrane Glycoproteins
  • RNA, Small Interfering
  • Viral Envelope Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • p17 protein, Human Immunodeficiency Virus Type 1
Topics
  • Adaptor Protein Complex 3 (physiology)
  • Adaptor Protein Complex delta Subunits (physiology)
  • Antigens, CD (analysis, metabolism)
  • Antigens, CD63
  • Antigens, CD81
  • Antigens, CD82 (analysis)
  • Antigens, CD9
  • Biological Transport (physiology)
  • CD4-Positive T-Lymphocytes (virology)
  • Cell Communication (physiology)
  • Coculture Techniques
  • Cytoplasmic Vesicles (chemistry, virology)
  • Dendritic Cells (metabolism, virology)
  • HIV Antigens (analysis)
  • HIV-1 (physiology)
  • HLA-DR Antigens (analysis)
  • Humans
  • Lysosome-Associated Membrane Glycoproteins (analysis)
  • Membrane Glycoproteins (analysis)
  • Membrane Proteins (analysis, metabolism)
  • Platelet Membrane Glycoproteins (analysis)
  • RNA, Small Interfering (genetics)
  • Viral Envelope Proteins (physiology)
  • Virion (chemistry, physiology)
  • Virus Replication (physiology)
  • gag Gene Products, Human Immunodeficiency Virus (analysis)

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