Nef is required for efficient HIV-1 replication in cocultures of dendritic cells and lymphocytes.
Dendritic cells (DCs) are thought to play a crucial role in the pathogenesis of HIV-1 infection. DCs are believed to transport virus particles to lymph nodes before transfer to CD4(+) lymphocytes. We have investigated the role of Nef in these processes. HIV-1 replication was examined in human immature DC-lymphocyte cocultures and in DCs or lymphocytes separately. Using various R5-tropic and X4-tropic HIV-1 strains and their nef-deleted (Deltanef) counterparts, we show that Nef is required for optimal viral replication in immature DC-T cells clusters and in T lymphocytes. Nef exerts only a marginal role on viral replication in immature DCs alone as well as on virion capture by DCs, long-term intracellular accumulation and transmission of X4 strains to lymphocytes. We also show that wild-type and Deltanef virions are similarly processed for MHC-I restricted exogenous presentation by DCs. Taken together, these results help explain how HIV-1 Nef may affect viral spread and immune responses in the infected host.
Petit
C
C
Unité Rétrovirus et Transfert Génétique, Laboratoire d'Immunopathologie Virale, URA CNRS 1930, Institut Pasteur, 28 rue du Dr Roux, Paris Cedex 15, 75724, France.
Buseyne
F
F
Boccaccio
C
C
Abastado
J P
JP
Heard
J M
JM
Schwartz
O
O
D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000473:pathology / Q000821:virology*; D015693:Gene Products, nef / Q000502:physiology*; D015658:HIV Infections / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000473:pathology / Q000821:virology*; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus