title: La Piedad Michoacán Mexico Virus V protein antagonizes type I interferon response by binding STAT2 protein and preventing STATs nuclear translocation.
abstract: La Piedad Michoacán Mexico Virus (LPMV) is a member of the Rubulavirus genus within the Paramyxoviridae family. LPMV is the etiologic agent of "blue eye disease", causing a significant disease burden in swine in Mexico with long-term implications for the agricultural industry. This virus mainly affects piglets and is characterized by meningoencephalitis and respiratory distress. It also affects adult pigs, causing reduced fertility and abortions in females, and orchitis and epididymitis in males. Viruses of the Paramyxoviridae family evade the innate immune response by targeting components of the interferon (IFN) signaling pathway. The V protein, expressed by most paramyxoviruses, is a well-characterized IFN signaling antagonist. Until now, there were no reports on the role of the LPMV-V protein in inhibiting the IFN response. In this study we demonstrate that LPMV-V protein antagonizes type I but not type II IFN signaling by binding STAT2, a component of the type I IFN cascade. Our results indicate that the last 18 amino acids of LPMV-V protein are required for binding to STAT2 in human and swine cells. While LPMV-V protein does not affect the protein levels of STAT1 or STAT2, it does prevent the IFN-induced phosphorylation and nuclear translocation of STAT1 and STAT2 thereby inhibiting cellular responses to IFN α/β.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States; Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via Federico Delpino 1, 80137 Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pisanelli
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States.
authors.forename: Maudry
authors.initials: M
authors.lastname: Laurent-Rolle
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States.
authors.forename: Balaji
authors.initials: B
authors.lastname: Manicassamy
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States.
authors.forename: Alan
authors.initials: A
authors.lastname: Belicha-Villanueva
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States.
authors.forename: Juliet
authors.initials: J
authors.lastname: Morrison
authors.affiliation: Departamento de Investigación y Desarrollo, Laboratorio Avi-Mex, SA de CV, Bartolache 1862, Colonia del Valle, D.F. México 01900, Mexico.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Lozano-Dubernard
authors.affiliation: Departamento de Investigación y Desarrollo, Laboratorio Avi-Mex, SA de CV, Bartolache 1862, Colonia del Valle, D.F. México 01900, Mexico.
authors.forename: Felipa
authors.initials: F
authors.lastname: Castro-Peralta
authors.affiliation: Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via Federico Delpino 1, 80137 Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Iovane
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States; Department of Medicine, Division of Infectious Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States. Electronic address: adolfo.garcia-sastre@mssm.edu.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D021381:Protein Transport; D019213:Rubulavirus / Q000276:immunology*; D050795:STAT2 Transcription Factor / Q000378:metabolism*; D013552:Swine; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; D050795:STAT2 Transcription Factor; D014764:Viral Proteins; C074576:V protein, Porcine rubulavirus
keywords: (LPMV) La Piedad Michoacan Mexico Virus; Interferon-signaling antagonist; LPMV-V; STAT2