MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

Menachery, Vineet D.; Mitchell, Hugh D.; Cockrell, Adam S.; Gralinski, Lisa E.; Yount, Jr., Boyd L.; Graham, Rachel L.; McAnarney, Eileen T.; Douglas, Madeline G.; Scobey, Trevor; Beall, Anne; Dinnon, III, Kenneth; Kocher, Jacob F.; Hale, Andrew E.; Stratton, Kelly G.; Waters, Katrina M.; Baric, Ralph S.; Racaniello, Vincent R.

doi:10.1128/mBio.00665-17

MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

Journal Article · Tue Aug 22 00:00:00 EDT 2017 · mBio (Online)

DOI:https://doi.org/10.1128/mBio.00665-17· OSTI ID:1406731

Menachery, Vineet D. ^[1]; Mitchell, Hugh D. ^[2]; Cockrell, Adam S. ^[3]; Gralinski, Lisa E. ^[3]; Yount, Jr., Boyd L. ^[3]; Graham, Rachel L. ^[3]; McAnarney, Eileen T. ^[3]; Douglas, Madeline G. ^[3]; Scobey, Trevor ^[3]; Beall, Anne ^[3]; Dinnon, III, Kenneth ^[3]; Kocher, Jacob F. ^[3]; Hale, Andrew E. ^[3]; Stratton, Kelly G. ^[2]; Waters, Katrina M. ^[2]; Baric, Ralph S. ^[3]; Racaniello, Vincent R. ^[4]

Univ. of Texas Medical Branch, Galveston, TX (United States); Univ. of North Carolina, Chapel Hill, NC (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Univ. of North Carolina, Chapel Hill, NC (United States)
Columbia Univ., New York, NY (United States)

While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation. In vitro replication attenuation also extends toin vivomodels, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward.

Here, the initial emergence and periodic outbreaks of MERS-CoV highlight a continuing threat posed by zoonotic pathogens to global public health. In these studies, mutant virus generation demonstrates the necessity of accessory ORFs in regard to MERS-CoV infection and pathogenesis. With this in mind, accessory ORF functions can be targeted for both therapeutic and vaccine treatments in response to MERS-CoV and related group 2C coronaviruses. In addition, disruption of accessory ORFs in parallel may offer a rapid response platform to attenuation of future emergent strains based on both SARS- and MERS-CoV accessory ORF mutants.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1406731

Report Number(s):: PNNL-SA--126255; WN9030198

Journal Information:: mBio (Online), Journal Name: mBio (Online) Journal Issue: 4 Vol. 8; ISSN 2150-7511

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

References (56)

Identification of Essential Genes as a Strategy to Select a Sars Candidate Vaccine Using a SARS-CoV Infectious cDNA Almazán, Fernando; De Diego, Marta L.; Galán, Carmen Advances in Experimental Medicine and Biology https://doi.org/10.1007/978-0-387-33012-9_105	book	January 2006
Two deletion variants of Middle East respiratory syndrome coronavirus found in a patient with characteristic symptoms Xie, Qian; Cao, Yujuan; Su, Juan Archives of Virology, Vol. 162, Issue 8 https://doi.org/10.1007/s00705-017-3361-x	journal	April 2017
Middle East respiratory syndrome Zumla, Alimuddin; Hui, David S.; Perlman, Stanley The Lancet, Vol. 386, Issue 9997 https://doi.org/10.1016/S0140-6736(15)60454-8	journal	September 2015
Host genetics of severe influenza: from mouse Mx1 to human IRF7 Ciancanelli, Michael J.; Abel, Laurent; Zhang, Shen-Ying Current Opinion in Immunology, Vol. 38 https://doi.org/10.1016/j.coi.2015.12.002	journal	February 2016
SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon Totura, Allison L.; Baric, Ralph S. Current Opinion in Virology, Vol. 2, Issue 3 https://doi.org/10.1016/j.coviro.2012.04.004	journal	June 2012
Cross host transmission in the emergence of MERS coronavirus Reusken, Chantal BEM; Raj, V. Stalin; Koopmans, Marion P. Current Opinion in Virology, Vol. 16 https://doi.org/10.1016/j.coviro.2016.01.004	journal	February 2016
Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches Okba, Nisreen MA; Raj, V. Stalin; Haagmans, Bart L. Current Opinion in Virology, Vol. 23 https://doi.org/10.1016/j.coviro.2017.03.007	journal	April 2017
A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses Spruth, Martin; Kistner, Otfried; Savidis-Dacho, Helga Vaccine, Vol. 24, Issue 5 https://doi.org/10.1016/j.vaccine.2005.08.055	journal	January 2006
Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor Ge, Xing-Yi; Li, Jia-Lu; Yang, Xing-Lou Nature, Vol. 503, Issue 7477 https://doi.org/10.1038/nature12711	journal	October 2013
A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease Graham, Rachel L.; Becker, Michelle M.; Eckerle, Lance D. Nature Medicine, Vol. 18, Issue 12 https://doi.org/10.1038/nm.2972	journal	November 2012
Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques Falzarano, Darryl; de Wit, Emmie; Rasmussen, Angela L. Nature Medicine, Vol. 19, Issue 10 https://doi.org/10.1038/nm.3362	journal	September 2013
A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence Menachery, Vineet D.; Yount, Boyd L.; Debbink, Kari Nature Medicine, Vol. 21, Issue 12 https://doi.org/10.1038/nm.3985	journal	November 2015
A mouse model for MERS coronavirus-induced acute respiratory distress syndrome Cockrell, Adam S.; Yount, Boyd L.; Scobey, Trevor Nature Microbiology, Vol. 2, Issue 2 https://doi.org/10.1038/nmicrobiol.2016.226	journal	November 2016
Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus Scobey, T.; Yount, B. L.; Sims, A. C. Proceedings of the National Academy of Sciences, Vol. 110, Issue 40 https://doi.org/10.1073/pnas.1311542110	journal	September 2013
SARS-like WIV1-CoV poised for human emergence Menachery, Vineet D.; Yount, Boyd L.; Sims, Amy C. Proceedings of the National Academy of Sciences, Vol. 113, Issue 11 https://doi.org/10.1073/pnas.1517719113	journal	March 2016
MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon- treatment de Wilde, A. H.; Raj, V. S.; Oudshoorn, D. Journal of General Virology, Vol. 94, Issue Pt_8 https://doi.org/10.1099/vir.0.052910-0	journal	April 2013
The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling Matthews, K. L.; Coleman, C. M.; van der Meer, Y. Journal of General Virology, Vol. 95, Issue Pt_4 https://doi.org/10.1099/vir.0.062059-0	journal	January 2014
Molecular Evolution of the SARS Coronavirus During the Course of the SARS Epidemic in China No authors listed Science, Vol. 303, Issue 5664, p. 1666-1669 https://doi.org/10.1126/science.1092002	journal	March 2004
An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels Haagmans, B. L.; van den Brand, J. M. A.; Raj, V. S. Science, Vol. 351, Issue 6268 https://doi.org/10.1126/science.aad1283	journal	December 2015
Protein-Protein Interactions Suggest Novel Activities of Human Cytomegalovirus Tegument Protein pUL103 Ortiz, Daniel A.; Glassbrook, James E.; Pellett, Philip E. Journal of Virology, Vol. 90, Issue 17 https://doi.org/10.1128/JVI.00097-16	journal	June 2016
Identification of Diverse Alphacoronaviruses and Genomic Characterization of a Novel Severe Acute Respiratory Syndrome-Like Coronavirus from Bats in China He, B.; Zhang, Y.; Xu, L. Journal of Virology, Vol. 88, Issue 12 https://doi.org/10.1128/JVI.00631-14	journal	April 2014
Characterization of a Novel Betacoronavirus Related to Middle East Respiratory Syndrome Coronavirus in European Hedgehogs Corman, V. M.; Kallies, R.; Philipps, H. Journal of Virology, Vol. 88, Issue 1 https://doi.org/10.1128/JVI.01600-13	journal	October 2013
Middle East Respiratory Syndrome Coronavirus Accessory Protein 4a Is a Type I Interferon Antagonist Niemeyer, D.; Zillinger, T.; Muth, D. Journal of Virology, Vol. 87, Issue 22 https://doi.org/10.1128/JVI.01845-13	journal	September 2013
Mechanisms of Zoonotic Severe Acute Respiratory Syndrome Coronavirus Host Range Expansion in Human Airway Epithelium Sheahan, T.; Rockx, B.; Donaldson, E. Journal of Virology, Vol. 82, Issue 5 https://doi.org/10.1128/JVI.02041-07	journal	December 2007
Release of Severe Acute Respiratory Syndrome Coronavirus Nuclear Import Block Enhances Host Transcription in Human Lung Cells Sims, A. C.; Tilton, S. C.; Menachery, V. D. Journal of Virology, Vol. 87, Issue 7 https://doi.org/10.1128/JVI.02520-12	journal	January 2013
Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus Yang, Xing-Lou; Hu, Ben; Wang, Bo Journal of Virology, Vol. 90, Issue 6 https://doi.org/10.1128/JVI.02582-15	journal	December 2015
Middle East Respiratory Syndrome Coronavirus 4a Protein Is a Double-Stranded RNA-Binding Protein That Suppresses PACT-Induced Activation of RIG-I and MDA5 in the Innate Antiviral Response Siu, K. -L.; Yeung, M. L.; Kok, K. -H. Journal of Virology, Vol. 88, Issue 9 https://doi.org/10.1128/JVI.03649-13	journal	February 2014
Host Regulatory Network Response to Infection with Highly Pathogenic H5N1 Avian Influenza Virus Li, C.; Bankhead, A.; Eisfeld, A. J. Journal of Virology, Vol. 85, Issue 21 https://doi.org/10.1128/JVI.05792-11	journal	August 2011
A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge Bolles, M.; Deming, D.; Long, K. Journal of Virology, Vol. 85, Issue 23 https://doi.org/10.1128/JVI.06048-11	journal	September 2011
Severe Acute Respiratory Syndrome Coronavirus Group-Specific Open Reading Frames Encode Nonessential Functions for Replication in Cell Cultures and Mice Yount, B.; Roberts, R. S.; Sims, A. C. Journal of Virology, Vol. 79, Issue 23 https://doi.org/10.1128/JVI.79.23.14909-14922.2005	journal	November 2005
Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus Josset, Laurence; Menachery, Vineet D.; Gralinski, Lisa E. mBio, Vol. 4, Issue 3 https://doi.org/10.1128/mBio.00165-13	journal	April 2013
Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation Thornbrough, Joshua M.; Jha, Babal K.; Yount, Boyd mBio, Vol. 7, Issue 2 https://doi.org/10.1128/mBio.00258-16	journal	March 2016
Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus Anthony, S. J.; Gilardi, K.; Menachery, V. D. mBio, Vol. 8, Issue 2 https://doi.org/10.1128/mBio.00373-17	journal	April 2017
Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential Kindler, Eveline; Jónsdóttir, Hulda R.; Muth, Doreen mBio, Vol. 4, Issue 1 https://doi.org/10.1128/mBio.00611-12	journal	February 2013
Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate Almazán, Fernando; DeDiego, Marta L.; Sola, Isabel mBio, Vol. 4, Issue 5 https://doi.org/10.1128/mBio.00650-13	journal	September 2013
Pathogenic Influenza Viruses and Coronaviruses Utilize Similar and Contrasting Approaches To Control Interferon-Stimulated Gene Responses Menachery, Vineet D.; Eisfeld, Amie J.; Schäfer, Alexandra mBio, Vol. 5, Issue 3 https://doi.org/10.1128/mBio.01174-14	journal	May 2014
Next-Generation High-Throughput Functional Annotation of Microbial Genomes Baric, Ralph S.; Crosson, Sean; Damania, Blossom mBio, Vol. 7, Issue 5 https://doi.org/10.1128/mBio.01245-16	journal	October 2016
Proteomic analysis of HIV-1 Gag interacting partners using proximity-dependent biotinylation Le Sage, Valerie; Cinti, Alessandro; Valiente-Echeverría, Fernando Virology Journal, Vol. 12, Issue 1 https://doi.org/10.1186/s12985-015-0365-6	journal	September 2015
Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine Jimenez-Guardeño, Jose M.; Regla-Nava, Jose A.; Nieto-Torres, Jose L. PLOS Pathogens, Vol. 11, Issue 10 https://doi.org/10.1371/journal.ppat.1005215	journal	October 2015
Middle East Respiratory Coronavirus Accessory Protein 4a Inhibits PKR-Mediated Antiviral Stress Responses Rabouw, Huib H.; Langereis, Martijn A.; Knaap, Robert C. M. PLOS Pathogens, Vol. 12, Issue 10 https://doi.org/10.1371/journal.ppat.1005982	journal	October 2016
Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation Boyd, Yount,; A., Goldstein, Stephen; Yize, Li, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/1xnb-9786	text	January 2016
A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease Eckerle, Lance D.; Baric, Ralph S.; Graham, Rachel L. The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/5x3m-6g75	text	January 2012
SARS-like WIV1-CoV poised for human emergence Kari, Debbink,; L., Graham, Rachel; E., Gralinski, Lisa The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/9tgz-an32	text	January 2016
Mechanisms of Zoonotic Severe Acute Respiratory Syndrome Coronavirus Host Range Expansion in Human Airway Epithelium Eric, Donaldson,; Timothy, Sheahan,; Davide, Corti, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/anq3-yj27	text	January 2008
Release of Severe Acute Respiratory Syndrome Coronavirus Nuclear Import Block Enhances Host Transcription in Human Lung Cells Chang, Jean; Luna, Maria L.; Matzke, Melissa M. American Society for Microbiology https://doi.org/10.17615/csc4-mq59	text	January 2013
A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge Long, Kristin; Bolles, Meagan; Baric, Ralph S. American Society for Microbiology https://doi.org/10.17615/e4vx-zc66	text	January 2011
Severe Acute Respiratory Syndrome Coronavirus Group-Specific Open Reading Frames Encode Nonessential Functions for Replication in Cell Cultures and Mice B., Frieman, Matthew; Boyd, Yount,; R., Denison, Mark The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/g9sk-6p87	text	January 2005
Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus Yount, Boyd L.; Menachery, Vineet D.; Graham, Rachel L. The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/kqa5-9507	text	January 2013
A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence Agnihothram, Sudhakar; Lanzavecchia, Antonio; Randell, Scott H. Nature America, Inc. https://doi.org/10.17615/kx4a-mx62	text	January 2015
A mouse model for MERS coronavirus-induced acute respiratory distress syndrome S., Cockrell, Adam; Xian-Chun, Tang,; Madeline, Douglas, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/kzxb-9b93	text	January 2016
Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus E., Gralinski, Lisa; Sudhakar, Agnihothram,; S., Carter, Victoria The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/mdjq-3337	text	January 2013
Pathogenic Influenza Viruses and Coronaviruses Utilize Similar and Contrasting Approaches To Control Interferon-Stimulated Gene Responses Tilton, Susan C.; Josset, Laurence; Menachery, Vineet D. American Society for Microbiology https://doi.org/10.17615/nabc-b354	text	January 2014
Deletion Variants of Middle East Respiratory Syndrome Coronavirus from Humans, Jordan, 2015 Lamers, Mart M.; Raj, V. Stalin; Shafei, Mah’d Emerging Infectious Diseases, Vol. 22, Issue 4 https://doi.org/10.3201/eid2204.152065	journal	April 2016
Middle East Respiratory Syndrome No authors listed https://doi.org/10.32388/rcto6j	posted_content	February 2020
Efficient replication of the novel human betacoronavirus EMC on primary human epithelium highlights its zoonotic potential. Kindler, Eveline; Jonsdottir, Hulda R.; Muth, Doreen American Society for Microbiology https://doi.org/10.7892/boris.122114	text	January 2013
Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus Anthony, Simon John; Gilardi, K.; Menachery, V. D. Columbia University https://doi.org/10.7916/d8vd8fmd	text	January 2017

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