HIV Type 1 Can Act as an APC upon Acquisition from the Host Cell of Peptide-Loaded HLA-DR and CD86 Molecules

Abstract

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-κB and NF-AT in an Ag-specific human T cell line. A linear correlation was found between activation of NF-κB 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.

Distinct host cell proteins incorporated by SIV replicating in CD4+T Cells from natural disease resistant versus non-natural disease susceptible hosts

“…One of the most important issues concerning these studies is the biological significance of the findings. Clearly as has been previously described the presence of virus-associated host proteins are of significant consequence as they can serve to a) promote cell to cell transmission of the virus [ 14 ], b) induce NF-κB and NFAT activation [ 16 ], c) the virions can act as antigen presenting cells since they contain both intact MHC class II and CD86 [ 73 ] and d) contain a long list of molecules involved in the induction and regulation of immune responses including HLA-Dr, ICAM-1, CD40, CD40L and CD86 [ 13 ]. In addition, select molecules present within these viruses also have been implicated in inducing immunosuppression and contributing to innocent bystander apoptosis highlighting the potential important role such host proteins can play in the pathogenesis of HIV/SIV infection.…”

Cellular proteins detected in HIV‐1

“…Several findings suggest a role for HLA-II in immunopathogenesis. HLA-II on virions is functional in that it can present both superantigen [70] and specific antigen [71] to CD4 T-cells. Chemically inactivated HIV-1 induces CD4 and CD8 T-cell apoptosis only when it contains HLA-II [72].…”

Efficient Replication of Human Immunodeficiency Virus Type 1 in Resting CD4+T Lymphocytes Is Induced by Coculture with Autologous Dendritic Cells in the Absence of Foreign Antigens

“…This can be mimicked using specific antibodies or paraformaldehyde-fixed cells expressing the necessary ligands such as HLA-DR, CD80, or CD86 (7,16). To define whether live iDC are needed for the increase in HIV-1 replication, resting CD4 ϩ T cells were exposed to HIV-1 and then cocultured either with live, heat-treated, or paraformaldehyde-fixed autologous iDC.…”