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Heterologous leukocyte-induced reactivation of HIV-1: implications for transfusion support of infected persons.
Busch M; Endow R; Lee TH; Sunzeri F; Louie L; Adams M; Perkins H; Vyas
December 30, 1990
Int Conf AIDS. 1990 Jun 20-23;6(3):138 (abstract no. S.A.227). Unique

OBJECTIVE: Evaluate possible cofactor role of heterologous blood components in reactivating HIV-1 infection. METHODS: Peripheral blood mononuclear cells (PBMC) from 3 asymptomatic anti-HIV-1-positive individuals were cultured and carefully monitored for HIV-1 proviral DNA titer using end-point dilution PCR and expression (RNA,p24 Ag) under the following conditions: 1) no stimulation (negative control); 2) phytohemagglutinin (PHA) stimulation (positive control); 3) coculture with 10(1) to 10(7) PHA-stimulated or non-stimulated, mitomicin C-treated (MCT) heterologous (HLA-matched and -mismatched) PBMC: 4) coculture with heterologous plasma, platelets, and RBC. RESULTS: MCT-heterologous PBMC induced a biphasic activation of HIV-1 expression: initial upregulation of viral gene expression in in vivo infected cells, followed by in vitro dissemination of infection to previously uninfected patent cells. Induction was dose-dependent; ratios of less than 1 stimulating cell to 10(3) patient PBMC were ineffective. Virus induction was enhanced by prior PHA-activation of the MCT heterologous PBMC. Both HLA-identical and mismatched PBMC induced reactivation. Enriched populations of activated monocytes were particularly effective inducers; 10% heterologous plasma showed slight induction; platelets and RBC showed no effect. CONCLUSION: These in vitro results suggest transfused heterologous PBMC may upregulate HIV-1 expression/replication in infected recipients.

Acquired Immunodeficiency Syndrome/*PATHOLOGY Blood Platelets/DRUG EFFECTS Blood Transfusion Cells, Cultured DNA, Viral/ANALYSIS Erythrocytes/DRUG EFFECTS Gene Expression Regulation, Viral Gene Products, gag/BIOSYNTHESIS/GENETICS Human *HIV-1/DRUG EFFECTS/GENETICS Leukocytes, Mononuclear/DRUG EFFECTS/*MICROBIOLOGY Lymphocyte Transformation Mitomycins/PHARMACOLOGY Phytohemagglutinins/PHARMACOLOGY Polymerase Chain Reaction RNA, Viral/BIOSYNTHESIS Up-Regulation (Physiology) Viral Core Proteins/BIOSYNTHESIS/GENETICS *Virus Activation Virus Replication ABSTRACT

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