Whitney, JamesAsmal, MohammedGeiben-Lynn, Ralf2011-12-052011Whitney, James B., Mohammed Asmal, and Ralf Geiben-Lynn. 2011. Serpin induced antiviral activity of prostaglandin synthetase-2 against HIV-1 replication. PLoS ONE 6(4): e18589.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:5360056The 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.en-USHIVinnate immunityhost-pathogen interactionclinical immunologyantiviralsinfectious diseasesJournal Article2011-12-0510.1371/journal.pone.0018589