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Title: Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species

Abstract

The regulation of the interferon type I (IFN-I) response has been shown to rely on posttranslational modification by ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15) to stabilize, or activate, a variety of IFN-I signaling and downstream effector proteins. Unlike Ub, which is almost perfectly conserved among eukaryotes, ISG15 is highly divergent, even among mammals. Since zoonotic viruses rely on viral proteins to recognize, or cleave, ISG15 conjugates in order to evade, or suppress, innate immunity, the impact of ISG15 biodiversity on deISGylating proteases of the ovarian tumor family (vOTU) from nairoviruses was evaluated. In this work, the enzymatic activities of vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, mice, shrews, sheep, bats, and camels, which are mammalian species known to be infected by nairoviruses. This along with investigation of binding by isothermal titration calorimetry illustrated significant differences in the abilities of nairovirus deISGylases to accommodate certain species of ISG15. To investigate the molecular underpinnings of species preferences of these vOTUs, a structure was determined to 2.5 Å for a complex of Erve virus vOTU protease and a mouse ISG15 domain. This structure revealed the molecularmore » basis of Erve virus vOTU's preference for ISG15 over Ub and the first structural insight into a nonhuman ISG15. This structure also revealed key interactions, or lack thereof, surrounding three amino acids that may drive a viral deISgylase to prefer an ISG15 from one species over that of another. Importance: Viral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of IFN-I signaling pathways. Unlike the case with ubiquitin, the amino acid sequences of ISG15s from various species are notably divergent. We illustrate that vOTUs have clear preferences for ISG15s from certain species. In addition, these observations are related to the molecular insights acquired via the first X-ray structure of the vOTU from the Erve nairovirus in complex with the first structurally resolved nonhuman ISG15. This information implicates certain amino acids that drive the preference of vOTUs for ISG15s from certain species.« less

Authors:
 [1];  [1];  [1];  [1]; ORCiD logo [1];  [1]; ORCiD logo [2];  [1]
  1. Univ. of Georgia, Athens, GA (United States)
  2. Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); USDA
OSTI Identifier:
1324784
Grant/Contract Number:  
W-31-109-Eng-38
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Virology
Additional Journal Information:
Journal Volume: 90; Journal Issue: 18; Journal ID: ISSN 0022-538X
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Deaton, M. K., Dzimianski, J. V., Daczkowski, C. M., Whitney, G. K., Mank, N. J., Parham, M. M., Bergeron, E., and Pegan, S. D. Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species. United States: N. p., 2016. Web. doi:10.1128/jvi.00975-16.
Deaton, M. K., Dzimianski, J. V., Daczkowski, C. M., Whitney, G. K., Mank, N. J., Parham, M. M., Bergeron, E., & Pegan, S. D. Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species. United States. https://doi.org/10.1128/jvi.00975-16
Deaton, M. K., Dzimianski, J. V., Daczkowski, C. M., Whitney, G. K., Mank, N. J., Parham, M. M., Bergeron, E., and Pegan, S. D. 2016. "Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species". United States. https://doi.org/10.1128/jvi.00975-16. https://www.osti.gov/servlets/purl/1324784.
@article{osti_1324784,
title = {Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species},
author = {Deaton, M. K. and Dzimianski, J. V. and Daczkowski, C. M. and Whitney, G. K. and Mank, N. J. and Parham, M. M. and Bergeron, E. and Pegan, S. D.},
abstractNote = {The regulation of the interferon type I (IFN-I) response has been shown to rely on posttranslational modification by ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15) to stabilize, or activate, a variety of IFN-I signaling and downstream effector proteins. Unlike Ub, which is almost perfectly conserved among eukaryotes, ISG15 is highly divergent, even among mammals. Since zoonotic viruses rely on viral proteins to recognize, or cleave, ISG15 conjugates in order to evade, or suppress, innate immunity, the impact of ISG15 biodiversity on deISGylating proteases of the ovarian tumor family (vOTU) from nairoviruses was evaluated. In this work, the enzymatic activities of vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, mice, shrews, sheep, bats, and camels, which are mammalian species known to be infected by nairoviruses. This along with investigation of binding by isothermal titration calorimetry illustrated significant differences in the abilities of nairovirus deISGylases to accommodate certain species of ISG15. To investigate the molecular underpinnings of species preferences of these vOTUs, a structure was determined to 2.5 Å for a complex of Erve virus vOTU protease and a mouse ISG15 domain. This structure revealed the molecular basis of Erve virus vOTU's preference for ISG15 over Ub and the first structural insight into a nonhuman ISG15. This structure also revealed key interactions, or lack thereof, surrounding three amino acids that may drive a viral deISgylase to prefer an ISG15 from one species over that of another. Importance: Viral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of IFN-I signaling pathways. Unlike the case with ubiquitin, the amino acid sequences of ISG15s from various species are notably divergent. We illustrate that vOTUs have clear preferences for ISG15s from certain species. In addition, these observations are related to the molecular insights acquired via the first X-ray structure of the vOTU from the Erve nairovirus in complex with the first structurally resolved nonhuman ISG15. This information implicates certain amino acids that drive the preference of vOTUs for ISG15s from certain species.},
doi = {10.1128/jvi.00975-16},
url = {https://www.osti.gov/biblio/1324784}, journal = {Journal of Virology},
issn = {0022-538X},
number = 18,
volume = 90,
place = {United States},
year = {Wed Jul 13 00:00:00 EDT 2016},
month = {Wed Jul 13 00:00:00 EDT 2016}
}

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Works referencing / citing this record:

ISG15 in antiviral immunity and beyond
journal, May 2018


Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies
journal, February 2018


Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement
journal, January 2019


Recent advances in understanding Crimean–Congo hemorrhagic fever virus
journal, January 2018


Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity
journal, January 2019


Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species
journal, June 2017


Structure and Function of Viral Deubiquitinating Enzymes
journal, November 2017


ISG15: It's Complicated
journal, October 2019


ISG15 in antiviral immunity and beyond
journal, May 2018


Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies
journal, February 2018


Recent advances in understanding Crimean–Congo hemorrhagic fever virus
journal, January 2018


Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions
journal, May 2017