Anti-viral activity of human antithrombin III.
Soluble inhibitory factors produced by CD8+ T-cells have been shown to inhibit HIV-1 replication and may play a critical role in vivo in anti-viral host defense. CD8+ T-cell-modified antithrombin III (ATIII) accounts for some of the described CD8+ T-cell anti-viral activity. We demonstrate that CD4+ T-cells, CD8+ T-cells, and natural killer cells react to an ATIII gradient by cell migration. Furthermore, exogenously added ATIII induced a G-protein-coupled signal transduction process in CD4+ T-cells and inhibited TNF-alpha-induced NF-kappaB activation. Heat and/or heparin treatment prior to the anti-viral inhibition test increased the anti-HIV activity up to 1000-fold. Our data indicate that anti-viral inactive ATIII can be activated having promising anti-viral properties as complementary candidate for the treatment of HIV infection.
Elmaleh
David R
DR
Division of Nuclear Medicine and Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA. delmaleh@partners.org
Brown
Nancy V
NV
Geiben-Lynn
Ralf
R
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000990:Antithrombin III / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development; D006493:Heparin / Q000737:chemistry; D006358:Hot Temperature; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019438:Ritonavir / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D015215:Zidovudine; D000990:Antithrombin III; D006493:Heparin; D008156:Luciferases; D019438:Ritonavir