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MERS-CoV papain-like protease has deISGylating and deubiquitinating activities.
Virology. 2014 Feb; 450-451:64-70.V

Abstract

Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection. Here, we investigate the predicted DUB activity of the PLpro domain of the recently described Middle East Respiratory Syndrome Coronavirus (MERS-CoV). We found that expression of MERS-CoV PLpro reduces the levels of ubiquitinated and ISGylated host cell proteins; consistent with multifunctional PLpro activity. Further, we compared the ability of MERS-CoV PLpro and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) PLpro to block innate immune signaling of proinflammatory cytokines. We show that expression of SARS-CoV and MERS-CoV PLpros blocks upregulation of cytokines CCL5, IFN-β and CXCL10 in stimulated cells. Overall these results indicate that the PLpro domains of MERS-CoV and SARS-CoV have the potential to modify the innate immune response to viral infection and contribute to viral pathogenesis.

Authors+Show Affiliations

Department Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine, 2160 S. First Ave., Maywood, IL 60153, USA.Department Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine, 2160 S. First Ave., Maywood, IL 60153, USA.Department of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, IN 47907, USA.Department of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, IN 47907, USA.Department Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine, 2160 S. First Ave., Maywood, IL 60153, USA. Electronic address: sbaker1@lumc.edu.

Pub Type(s)

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

Language

eng

PubMed ID

24503068

Citation

Mielech, Anna M., et al. "MERS-CoV Papain-like Protease Has deISGylating and Deubiquitinating Activities." Virology, vol. 450-451, 2014, pp. 64-70.
Mielech AM, Kilianski A, Baez-Santos YM, et al. MERS-CoV papain-like protease has deISGylating and deubiquitinating activities. Virology. 2014;450-451:64-70.
Mielech, A. M., Kilianski, A., Baez-Santos, Y. M., Mesecar, A. D., & Baker, S. C. (2014). MERS-CoV papain-like protease has deISGylating and deubiquitinating activities. Virology, 450-451, 64-70. https://doi.org/10.1016/j.virol.2013.11.040
Mielech AM, et al. MERS-CoV Papain-like Protease Has deISGylating and Deubiquitinating Activities. Virology. 2014;450-451:64-70. PubMed PMID: 24503068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MERS-CoV papain-like protease has deISGylating and deubiquitinating activities. AU - Mielech,Anna M, AU - Kilianski,Andy, AU - Baez-Santos,Yahira M, AU - Mesecar,Andrew D, AU - Baker,Susan C, Y1 - 2013/12/22/ PY - 2013/09/12/received PY - 2013/10/13/revised PY - 2013/11/26/accepted PY - 2014/2/8/entrez PY - 2014/2/8/pubmed PY - 2014/5/3/medline KW - DUB activity KW - ISG15 KW - MERS-CoV KW - PLpro KW - Ubiquitin KW - deISGylating activity SP - 64 EP - 70 JF - Virology JO - Virology VL - 450-451 N2 - Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection. Here, we investigate the predicted DUB activity of the PLpro domain of the recently described Middle East Respiratory Syndrome Coronavirus (MERS-CoV). We found that expression of MERS-CoV PLpro reduces the levels of ubiquitinated and ISGylated host cell proteins; consistent with multifunctional PLpro activity. Further, we compared the ability of MERS-CoV PLpro and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) PLpro to block innate immune signaling of proinflammatory cytokines. We show that expression of SARS-CoV and MERS-CoV PLpros blocks upregulation of cytokines CCL5, IFN-β and CXCL10 in stimulated cells. Overall these results indicate that the PLpro domains of MERS-CoV and SARS-CoV have the potential to modify the innate immune response to viral infection and contribute to viral pathogenesis. SN - 1096-0341 UR - https://www.unboundmedicine.com/medline/citation/24503068/MERS_CoV_papain_like_protease_has_deISGylating_and_deubiquitinating_activities_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(13)00662-4 DB - PRIME DP - Unbound Medicine ER -