title: Prostaglandin A1 inhibits avian influenza virus replication at a postentry level: Effect on virus protein synthesis and NF-κB activity.
abstract: Influenza A viruses (IAV) have the potential to cause devastating pandemics. In recent years, the emergence of new avian strains able to infect humans represents a serious threat to global human health. The increase in drug-resistant IAV strains underscores the need for novel approaches to anti-influenza chemotherapy. Herein we show that prostaglandin-A1 (PGA1) possesses antiviral activity against avian IAV, including H5N9, H7N1 and H1N1 strains, acting at a level different from the currently available anti-influenza drugs. PGA1 acts at postentry level, causing dysregulation of viral protein synthesis and preventing virus-induced disassembly of host microtubular network and activation of pro-inflammatory factor NF-κB. The antiviral activity is dependent on the presence of a cyclopentenone ring structure and is associated with activation of a cytoprotective heat shock response in infected cells. The results suggest that cyclopentenone prostanoids or prostanoids-derived molecules may represent a new tool to combat avian influenza virus infection.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Carta
authors.affiliation: Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: La Frazia
authors.affiliation: Department of Infectious Diseases, Istituto Superiore di Sanita', 00161 Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Donatelli
authors.affiliation: Department of Infectious Diseases, Istituto Superiore di Sanita', 00161 Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Puzelli
authors.affiliation: Institute of Translational Pharmacology, CNR, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy; Institute of Translational Pharmacology, CNR, Rome, Italy. Electronic address: santoro@bio.uniroma2.it.
authors.forename: M Gabriella
authors.initials: MG
authors.lastname: Santoro
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002645:Chickens; D004285:Dogs; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000502:physiology; D057916:Influenza A Virus, H7N1 Subtype / Q000187:drug effects / Q000502:physiology; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D061985:Madin Darby Canine Kidney Cells; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D011454:Prostaglandins A / Q000494:pharmacology*; D011650:Pulmonary Alveoli; D014764:Viral Proteins / Q000096:biosynthesis*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D016328:NF-kappa B; D011454:Prostaglandins A; D014764:Viral Proteins; C100573:prostaglandin A1
keywords: Antiviral; Cyclopentenone prostanoids; Heat shock proteins; NF-kappaB