Novel Bat Influenza Virus NS1 Proteins Bind Double-Stranded RNA and Antagonize Host Innate Immunity

Hannah L Turkington; Mindaugas Juozapaitis; Philip S Kerry; Teresa Aydillo; Juan Ayllon; Adolfo García-Sastre; Martin Schwemmle; Benjamin G Hale

doi:10.1128/JVI.01430-15

Novel Bat Influenza Virus NS1 Proteins Bind Double-Stranded RNA and Antagonize Host Innate Immunity

J Virol. 2015 Oct;89(20):10696-701. doi: 10.1128/JVI.01430-15. Epub 2015 Aug 5.

Authors

Hannah L Turkington¹, Mindaugas Juozapaitis², Philip S Kerry³, Teresa Aydillo⁴, Juan Ayllon⁴, Adolfo García-Sastre⁵, Martin Schwemmle⁶, Benjamin G Hale⁷

Affiliations

¹ Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
² Institute of Virology, Center for Microbiology and Hygiene, University Medical Center Freiburg, Freiburg, Germany.
³ Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, Fife, United Kingdom.
⁴ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶ Institute of Virology, Center for Microbiology and Hygiene, University Medical Center Freiburg, Freiburg, Germany [email protected] [email protected].
⁷ Institute of Medical Virology, University of Zurich, Zurich, Switzerland [email protected] [email protected].

Abstract

We demonstrate that novel bat HL17NL10 and HL18NL11 influenza virus NS1 proteins are effective interferon antagonists but do not block general host gene expression. Solving the RNA-binding domain structures revealed the canonical NS1 symmetrical homodimer, and RNA binding required conserved basic residues in this domain. Interferon antagonism was strictly dependent on RNA binding, and chimeric bat influenza viruses expressing NS1s defective in this activity were highly attenuated in interferon-competent cells but not in cells unable to establish antiviral immunity.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chiroptera / virology*
Gene Expression Regulation
Host-Pathogen Interactions
Immunity, Innate
Influenza A virus / genetics*
Influenza A virus / immunology
Interferon-beta / genetics
Interferon-beta / immunology
Models, Molecular
Orthomyxoviridae Infections / genetics
Orthomyxoviridae Infections / immunology
Orthomyxoviridae Infections / veterinary*
Orthomyxoviridae Infections / virology
Protein Binding
Protein Isoforms / chemistry
Protein Isoforms / genetics
Protein Isoforms / immunology
Protein Structure, Secondary
Protein Structure, Tertiary
RNA, Double-Stranded / chemistry*
RNA, Double-Stranded / immunology
RNA, Double-Stranded / metabolism
RNA-Binding Proteins / chemistry*
RNA-Binding Proteins / genetics
RNA-Binding Proteins / immunology
Signal Transduction
Viral Nonstructural Proteins / chemistry*
Viral Nonstructural Proteins / genetics
Viral Nonstructural Proteins / immunology
Virus Replication

Substances

INS1 protein, influenza virus
Protein Isoforms
RNA, Double-Stranded
RNA-Binding Proteins
Viral Nonstructural Proteins
Interferon-beta

Abstract

Publication types

MeSH terms

Substances

Grants and funding