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Cell Rep. 2018 Jul 24;24(4):861-872.e6. doi: 10.1016/j.celrep.2018.06.045.

Conservation of Structure and Immune Antagonist Functions of Filoviral VP35 Homologs Present in Microbat Genomes.

Author information

1
Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
2
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
4
Cornell College, Mt. Vernon, IA 52314, USA; Industrial Macromolecular Crystallography Association-Collaborative Access Team, Hauptman-Woodward Medical Research Institute, Buffalo, NY 14203, USA.
5
Industrial Macromolecular Crystallography Association-Collaborative Access Team, Hauptman-Woodward Medical Research Institute, Buffalo, NY 14203, USA.
6
Institute of Immunology, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institute, Südufer 10, 17493 Greifswald-Insel Riems, Germany.
7
Department of Biological Sciences, The State University of New York at Buffalo, Buffalo, NY 14260, USA. Electronic address: djtaylor@buffalo.edu.
8
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: dwleung@wustl.edu.
9
Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. Electronic address: cbasler@gsu.edu.

Abstract

Non-retroviral integrated RNA viral sequences (NIRVs) potentially encoding ∼280 amino acid homologs to filovirus VP35 proteins are present across the Myotis genus of bats. These are estimated to have been maintained for ∼18 million years, indicating their co-option. To address the reasons for co-option, 16 Myotis VP35s were characterized in comparison to VP35s from the extant filoviruses Ebola virus and Marburg virus, in which VP35s play critical roles in immune evasion and RNA synthesis. The Myotis VP35s demonstrated a conserved suppression of innate immune signaling, albeit with reduced potency, in either human or Myotis cells. Their attenuation reflects a lack of dsRNA binding that in the filoviral VP35s correlates with potent suppression of interferon responses. Despite divergent function, evolution has preserved in Myotis the structure of the filoviral VP35s, indicating that this structure is critical for co-opted function, possibly as a regulator of innate immune signaling.

KEYWORDS:

Ebola virus; Marburg virus; Myotis bats; VP35; evolution; filovirus; non-retroviral integrated RNA viral sequence

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