HIV type 1 can act as an APC upon acquisition from the host cell of peptide-loaded HLA-DR and CD86 molecules.
It is well documented that a wide range of host-derived cell surface constituents is inserted within HIV type 1 (HIV-1) and located on the exterior of the virion. Although no virus-associated protein of host origin has been shown to be absolutely required for virus replication, studies have revealed that many of these proteins are functional and can affect several steps of the virus life cycle. In this study, we found that HIV-1 acquires peptide-loaded class II MHC (MHC-II) and the costimulatory CD86 molecules from the host cell. Moreover, we present evidence that virions bearing such peptide-loaded MHC-II and CD86 proteins can lead to activation of the transcription factors NF-kappa B and NF-AT in an Ag-specific human T cell line. A linear correlation was found between activation of NF-kappa B and the amount of peptide-loaded MHC-II molecules inserted within HIV-1. Finally, transcription of unintegrated and integrated HIV-1 DNA was promoted upon exposure of peptide-specific human T cells to viruses bearing both peptide-loaded MHC-II and CD86 proteins. These data suggest that HIV-1 can operate as an APC depending on the nature of virus-anchored host cell membrane components. It can be proposed that HIV-1 can manipulate one of its primary targets through the process of incorporation of host-derived proteins.
Roy
Jocelyn
J
Research Center in Infectious Diseases, Centre Hospitalier de l'Université Laval Research Center, and Faculty of Medicine, Laval University, Quebec, Canada.
Martin
Geneviève
G
Giguère
Jean-François
JF
Bélanger
Dave
D
Pétrin
Myriam
M
Tremblay
Michel J
MJ
D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000821:virology*; D015703:Antigens, CD / Q000378:metabolism*; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D022142:Secretory Vesicles / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014158:Transcription, Genetic
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D016328:NF-kappa B