Serpin induced antiviral activity of prostaglandin synthetase-2 against HIV-1 replication

• Published in: PloS one 2011-04, Vol.6 (4), p.e18589-e18589
• Main Authors: Whitney, James B, Asmal, Mohammed, Geiben-Lynn, Ralf
• Format: Article
• Language: English
• Subjects: Adenosine; Anticoagulants; Antithrombin; Antiviral activity; Antiviral agents; Antiviral Agents - metabolism; Biology; Blotting, Western; Cell culture; Cellular signal transduction; Clinical trials; Cloning; Cytotoxicity; Diabetes; Enzyme-Linked Immunosorbent Assay; Gene expression; Genes; Genomes; Heparin; Hepatitis; Hepatitis C virus; Herpes viruses; HIV; HIV-1 - physiology; Human immunodeficiency virus; Infections; Inflammation; Ligases; Measles; Medical schools; Medicine; Overexpression; Pathogenesis; Peripheral blood mononuclear cells; Prostaglandin-Endoperoxide Synthases - metabolism; Prostaglandins; Protease inhibitors; Proteinase inhibitors; Proteins; Replication; Serine; Serine proteinase; Serine proteinase inhibitors; Serpins; Serpins - physiology; Signal Transduction; Thrombin; Transcription; Transduction; Viral infections; Virus replication; Virus Replication - physiology; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0018589

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.