title: Allogeneic leukocytes but not therapeutic blood elements induce reactivation and dissemination of latent human immunodeficiency virus type 1 infection: implications for transfusion support of infected patients.
abstract: Various immunologic stimuli and heterologous viral regulatory elements have been shown to increase susceptibility to, and replication of, human immunodeficiency virus type 1 (HIV-1) in lymphocytes and monocytes in vitro. Transfusion of allogeneic blood components from heterologous donors constitutes a profound immunologic stimulus to the recipient, in addition to being a potential route of transmission of lymphotropic viral infections. To investigate the hypothesis that transfusions, and particularly those containing leukocytes, activate HIV-1 replication in infected recipient cells, we cocultured peripheral blood mononuclear cells (PBMC) from three anti-HIV-1-positive individuals with allogeneic donor PBMC, as well as partially purified populations of donor lymphocytes, monocytes, granulocytes, platelets, and red blood cells (RBC) and allogeneic cell-free plasma. Allogeneic PBMC induced a dose-related activation of HIV-1 expression in in vivo infected cells, followed by dissemination of HIV-1 to previously uninfected patient cells. Activation of HIV-1 replication was observed with donor lymphocytes, monocytes, and granulocytes, whereas no effect was seen with leukocyte-depleted RBC, platelets, or plasma (ie, therapeutic blood constituents). Allogeneic donor PBMC were also shown to upregulate HIV-1 expression in a "latently" infected cell line, and to increase susceptibility of heterologous donor PBMC to acute HIV-1 infection. Studies should be performed to evaluate whether transfusions of leukocyte-containing blood components accelerate HIV-1 dissemination and disease progression in vivo. If so, HIV-1-infected patients should be transfused as infrequently as possible and leukocyte-depleted (filtered) blood components should be used to avoid this complication.
authors.affiliation: Irwin Memorial Blood Centers, San Francisco, CA 94118.
authors.forename: M P
authors.initials: MP
authors.lastname: Busch
authors.forename: T H
authors.initials: TH
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Heitman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000628:therapy; D016913:Blood Component Transfusion; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D006098:Granulocytes / Q000502:physiology; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology* / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D065227:Transfusion Reaction; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D016655:HIV Core Protein p24