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108 A Novel Virus Capture Assay Reveals a Differential Acquisition of Host HLA-DR by Clinical Strains of HIV-1 Expanded in Primary Human Cells Depending on the Nature of Producing Cells and Donor Source
G. Martin*, R. Cantin, and M. Tremblay
Univ. Laval, Sainte-Foy, Québec, Canada
Background: Previous findings indicated that HLA-DR is probably 1 of the most abundant host cell constituents incorporated within the human immunodeficiency virus type 1 (HIV-1) envelope. These observations raise the possibility of immunizing individuals against allogenic non-self MHC molecules. This strategy could potentially provide an efficient protection against HIV-1 infection.
Methods: A novel viral capture technique using immunomagnetic beads was developed to assess the frequency of virions bearing foreign HLA-DR. We tested several clinical isolates of HIV-1 derived from primary human peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDM).
Results: Analysis of virus stocks purified from PBMCs and MDM indicated that primary strains of HIV-1 bearing distinct tropism (i.e., T-, macrophage-, and dual-tropic) do all incorporate host cell membrane HLA-DR. Propagation of some clinical HIV-1 strains in either autologous PBMCs or MDM resulted in differences in the frequency of HLA-DR-bearing virions depending of the nature of virus producer cells. Moreover, the proportion of HIV-1 particles that contains host-derived HLA-DR in their envelope was also influenced by the donor source.
Conclusions: Altogether these data show that the efficiency of HLA-DR incorporation in the envelope of primary isolates of HIV-1 is a multifactorial phenomenon since it is affected by the nature of host cells (i.e., PBMCs or MDM) and the donor source (i.e., genetic background). We strongly believe that the incorporation process of several functional foreign proteins within mature HIV-1 particles can be exploited to enhance the potency of HIV-1 immunogen.
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