Purification of a modified form of bovine antithrombin III as an HIV-1 CD8+ T-cell antiviral factor.
CD8(+) T-cells secrete soluble factor(s) capable of inhibiting both R5- and X4-tropic strains of human immunodeficiency virus type 1 (HIV-1). CCR5 chemokine ligands, released from activated CD8(+) T-cells, contribute to the antiviral activity of these cells. These CC-chemokines, however, do not account for all CD8(+) T-cell antiviral factor(s) (CAF) released from these cells, particularly because the elusive CAF can inhibit the replication of X4 HIV-1 strains that use CXCR4 and not CCR5 as a coreceptor. Here we demonstrate that activated CD8(+) T-cells of HIV-1-seropositive individuals modify serum bovine antithrombin III into an HIV-1 inhibitory factor capable of suppressing the replication of X4 HIV-1. These data indicate that antithrombin III may play a role in the progression of HIV-1 disease.
Partners AIDS Research Center, Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston 02129, USA.
Ralf
R
Geiben-Lynn
Nancy
N
Brown
Bruce D
BD
Walker
Andrew D
AD
Luster
D000818:Animals; D000990:Antithrombin III / Q000302:isolation & purification* / Q000494:pharmacology; D000998:Antiviral Agents / Q000302:isolation & purification*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D000990:Antithrombin III