La Piedad Michoacán Mexico Virus V protein antagonizes type I interferon response by binding STAT2 protein and preventing STATs nuclear translocation

Giuseppe Pisanelli; Maudry Laurent-Rolle; Balaji Manicassamy; Alan Belicha-Villanueva; Juliet Morrison; Bernardo Lozano-Dubernard; Felipa Castro-Peralta; Giuseppe Iovane; Adolfo García-Sastre

doi:10.1016/j.virusres.2015.10.027

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La Piedad Michoacán Mexico Virus V protein antagonizes type I interferon response by binding STAT2 protein and preventing STATs nuclear translocation

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La Piedad Michoacán Mexico Virus V protein antagonizes type I interferon response by binding STAT2 protein and preventing STATs nuclear translocation

Giuseppe Pisanelli, Maudry Laurent-Rolle, Balaji Manicassamy, Alan Belicha-Villanueva, Juliet Morrison, Bernardo Lozano-Dubernard, Felipa Castro-Peralta, Giuseppe Iovane and Adolfo García-Sastre

Virus research, Vol.213, pp.11-22

02/02/2016

DOI: 10.1016/j.virusres.2015.10.027

PMCID: PMC5538256

PMID: 26546155

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Abstract

•La Piedad Michoacán Mexico Virus (LPMV) V protein antagonizes type I but not type II IFN signaling.•Type I IFN interferon-signaling inhibition is due to the binding with LPMV-V protein with STAT2 protein, a fundamental component of type I IFN cascade.•LPMV-V protein does prevent the IFN-induced phosphorylation and nuclear translocation of STAT1 and STAT2 thereby inhibiting cellular responses to IFN α/β.•The last 18 amino acids are necessary for binding to STAT2 in human and swine origin cells. 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.

Interferon-signaling antagonist

(LPMV) La Piedad Michoacan Mexico Virus

LPMV-V

STAT2

Details

Title: Subtitle: La Piedad Michoacán Mexico Virus V protein antagonizes type I interferon response by binding STAT2 protein and preventing STATs nuclear translocation
Creators: Giuseppe Pisanelli - Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States
Maudry Laurent-Rolle - Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States
Balaji Manicassamy - Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States
Alan Belicha-Villanueva - Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States
Juliet Morrison - Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States
Bernardo Lozano-Dubernard - Departamento de Investigación y Desarrollo, Laboratorio Avi-Mex, SA de CV, Bartolache 1862, Colonia del Valle, D.F. México 01900, Mexico
Felipa Castro-Peralta - Departamento de Investigación y Desarrollo, Laboratorio Avi-Mex, SA de CV, Bartolache 1862, Colonia del Valle, D.F. México 01900, Mexico
Giuseppe Iovane - Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via Federico Delpino 1, 80137 Naples, Italy
Adolfo García-Sastre - Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States
Resource Type: Journal article
Publication Details: Virus research, Vol.213, pp.11-22
DOI: 10.1016/j.virusres.2015.10.027
PMID: 26546155
PMCID: PMC5538256
NLM abbreviation: Virus Res
ISSN: 0168-1702
eISSN: 1872-7492
Publisher: Elsevier B.V
Grant note: DOI: 10.13039/100000060, name: NIAID, award: U19AI083025; name: National Institute of Health Fellowship
Language: English
Date published: 02/02/2016
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083286202771

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