title: Serpin induced antiviral activity of prostaglandin synthetase-2 against HIV-1 replication.
abstract: The serine protease inhibitors (serpins) are anti-inflammatory proteins that have various functions. By screening a diverse panel of viruses, we demonstrate that the serpin antithrombin III (ATIII) has a broad-spectrum anti-viral activity for HIV-1, HCV and HSV. To investigate the mechanism of action in more detail we investigated the HIV-1 inhibition. Using gene-expression arrays we found that multiple host cell signal transduction pathways were activated by ATIII in HIV-1 infected cells but not in uninfected controls. Moreover, the signal pathways initiated by ATIII treatment, were more than 200-fold increased by the use of heparin-activated ATIII. The most up-regulated transcript in HIV-1 infected cells was prostaglandin synthetase-2 (PTGS2). Furthermore, we found that over-expression of PTGS2 reduced levels of HIV-1 replication in human PBMC. These findings suggest a central role for serpins in the host innate anti-viral response. Host factors such as PTGS2 elicited by ATIII treatment could be exploited in the development of novel anti-viral interventions.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: James B
authors.initials: JB
authors.lastname: Whitney
authors.forename: Mohammed
authors.initials: M
authors.lastname: Asmal
authors.forename: Ralf
authors.initials: R
authors.lastname: Geiben-Lynn
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D015843:Serpins / Q000502:physiology*; D015398:Signal Transduction; D014779:Virus Replication / Q000502:physiology*
chemical_list: D000998:Antiviral Agents; D015843:Serpins; D011451:Prostaglandin-Endoperoxide Synthases