Dysregulation of lung epithelial cell homeostasis and immunity contributes to Middle East respiratory syndrome coronavirus disease severity

Sims, Amy C.; Schäfer, Alexandra; Okuda, Kenichi; Leist, Sarah R.; Kocher, Jacob F.; Cockrell, Adam S.; Hawkins, Padraig E.; Furusho, Minako; Jensen, Kara L.; Kyle, Jennifer E.; Burnum-Johnson, Kristin E.; Stratton, Kelly G.; Lamar, Natalie C.; Niccora, Carrie D.; Weitz, Karl K.; Smith, Richard D.; Metz, Thomas O.; Waters, Katrina M.; Boucher, Richard C.; Montgomery, Stephanie A.; Baric, Ralph S.; Sheahan, Timothy P.

doi:10.1128/msphere.00951-24

Title: Dysregulation of lung epithelial cell homeostasis and immunity contributes to Middle East respiratory syndrome coronavirus disease severity

Journal Article · Thu Jan 30 00:00:00 UTC 2025 · mSphere

DOI: https://doi.org/10.1128/msphere.00951-24 · OSTI ID:2581056

Sims, Amy C. ^[1]; Schäfer, Alexandra ^[1]; Okuda, Kenichi ^[1]; Leist, Sarah R. ^[1]; Kocher, Jacob F. ^[1]; Cockrell, Adam S. ^[1]; Hawkins, Padraig E. ^[1]; Furusho, Minako ^[1]; Jensen, Kara L. ^[1]; Kyle, Jennifer E. ^[2];

^[2];

^[2]; Smith, Richard D. ^[2];

^[2];

^[2]; Boucher, Richard C. ^[1]; Montgomery, Stephanie A. ^[1] more »

University of North Carolina, Chapel Hill, NC (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Coronaviruses (CoV) emerge suddenly from animal reservoirs to cause novel diseases in new hosts. Discovered in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in camels in the Middle East and is continually causing local outbreaks and epidemics. While all three newly emerging human CoVs from the past 20 years (SARS-CoV, SARS-CoV-2, and MERS-CoV) cause respiratory disease, each CoV has unique host interactions that drive differential pathogeneses. To better understand the virus and host interactions driving lethal MERS-CoV infection, we performed a longitudinal multi-omics analysis of sublethal and lethal MERS-CoV infection in mice. Significant differences were observed in body weight loss, virus titers, and acute lung injury among lethal and sub-lethal virus doses. Virus-induced apoptosis of type I and II alveolar epithelial cells suggests that loss or dysregulation of these key cell populations was a major driver of severe disease. Omics analysis suggested differential pathogenesis was multi-factorial with clear differences among innate and adaptive immune pathways as well as those that regulate lung epithelial homeostasis. Infection of mice lacking functional T and B cells showed that adaptive immunity was important in controlling viral replication but also increased pathogenesis. In summary, we provide a high-resolution host response atlas for MERS-CoV infection and disease severity. Multi-omics studies of viral pathogenesis offer a unique opportunity to not only better understand the molecular mechanisms of disease but also to identify genes and pathways that can be exploited for therapeutic intervention all of which is important for our future pandemic preparedness.

View Accepted Manuscript (DOE)

Cite

Export

Save

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

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2581056

Report Number(s):: PNNL-SA--204428

Journal Information:: mSphere, Journal Name: mSphere Journal Issue: 2 Vol. 10; ISSN 2379-5042

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

References (70)

Metabolite, Protein, and Lipid Extraction (MPLEx): A Method that Simultaneously Inactivates Middle East Respiratory Syndrome Coronavirus and Allows Analysis of Multiple Host Cell Components Following Infection Nicora, Carrie D.; Sims, Amy C.; Bloodsworth, Kent J. Methods in Molecular Biology https://doi.org/10.1007/978-1-0716-0211-9_14	book	December 2019
Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study Müller, Marcel A.; Meyer, Benjamin; Corman, Victor M. The Lancet Infectious Diseases, Vol. 15, Issue 5 https://doi.org/10.1016/S1473-3099(15)70090-3	journal	May 2015
Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics Petersen, Eskild; Koopmans, Marion; Go, Unyeong The Lancet Infectious Diseases, Vol. 20, Issue 9 https://doi.org/10.1016/S1473-3099(20)30484-9	journal	September 2020
Middle East respiratory syndrome coronavirus transmission among health care workers: Implication for infection control Alfaraj, Sarah H.; Al-Tawfiq, Jaffar A.; Altuwaijri, Talal A. American Journal of Infection Control, Vol. 46, Issue 2 https://doi.org/10.1016/j.ajic.2017.08.010	journal	February 2018
Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 Ng, Dianna L.; Al Hosani, Farida; Keating, M. Kelly The American Journal of Pathology, Vol. 186, Issue 3 https://doi.org/10.1016/j.ajpath.2015.10.024	journal	March 2016
An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity Baseler, Laura J.; Falzarano, Darryl; Scott, Dana P. The American Journal of Pathology, Vol. 186, Issue 3 https://doi.org/10.1016/j.ajpath.2015.10.025	journal	March 2016
The multifaceted roles of the invariant chain CD74 — More than just a chaperone Schröder, Bernd Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1863, Issue 6 https://doi.org/10.1016/j.bbamcr.2016.03.026	journal	June 2016
Restoring pulmonary surfactant membranes and films at the respiratory surface Echaide, Mercedes; Autilio, Chiara; Arroyo, Raquel Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1859, Issue 9 https://doi.org/10.1016/j.bbamem.2017.03.015	journal	September 2017
A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice Leist, Sarah R.; Dinnon, Kenneth H.; Schäfer, Alexandra Cell, Vol. 183, Issue 4 https://doi.org/10.1016/j.cell.2020.09.050	journal	November 2020
A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry Chen, Jing; Yang, Xinglou; Si, Haorui Cell, Vol. 186, Issue 4 https://doi.org/10.1016/j.cell.2023.01.019	journal	February 2023
Superspreading and heterogeneity in transmission of SARS, MERS, and COVID-19: A systematic review Wang, Jingxuan; Chen, Xiao; Guo, Zihao Computational and Structural Biotechnology Journal, Vol. 19 https://doi.org/10.1016/j.csbj.2021.08.045	journal	January 2021
Inverse Correlation of TRIM32 and Protein Kinase C ζ in T Helper Type 2–Biased Inflammation Wang, Zhiping; Yoo, Yeon Jung; De La Torre, Rachel Journal of Investigative Dermatology, Vol. 141, Issue 5 https://doi.org/10.1016/j.jid.2020.09.021	journal	May 2021
Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease Douglas, Madeline G.; Kocher, Jacob F.; Scobey, Trevor Virology, Vol. 517 https://doi.org/10.1016/j.virol.2017.12.006	journal	April 2018
Combined Statistical Analyses of Peptide Intensities and Peptide Occurrences Improves Identification of Significant Peptides from MS-Based Proteomics Data Webb-Robertson, Bobbie-Jo M.; McCue, Lee Ann; Waters, Katrina M. Journal of Proteome Research, Vol. 9, Issue 11 https://doi.org/10.1021/pr1005247	journal	November 2010
Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC Raj, V. Stalin; Mou, Huihui; Smits, Saskia L. Nature, Vol. 495, Issue 7440 https://doi.org/10.1038/nature12005	journal	March 2013
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
Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq Treutlein, Barbara; Brownfield, Doug G.; Wu, Angela R. Nature, Vol. 509, Issue 7500 https://doi.org/10.1038/nature13173	journal	April 2014
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
SARS and MERS: recent insights into emerging coronaviruses de Wit, Emmie; van Doremalen, Neeltje; Falzarano, Darryl Nature Reviews Microbiology, Vol. 14, Issue 8 https://doi.org/10.1038/nrmicro.2016.81	journal	June 2016
Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV Sheahan, Timothy P.; Sims, Amy C.; Leist, Sarah R. Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-019-13940-6	journal	January 2020
Close relatives of MERS-CoV in bats use ACE2 as their functional receptors Xiong, Qing; Cao, Lei; Ma, Chengbao Nature, Vol. 612, Issue 7941 https://doi.org/10.1038/s41586-022-05513-3	journal	December 2022
A compendium of multi-omics data illuminating host responses to lethal human virus infections Eisfeld, Amie J.; Anderson, Lindsey N.; Fan, Shufang Scientific Data, Vol. 11, Issue 1 https://doi.org/10.1038/s41597-024-03124-3	journal	April 2024
Cell type-resolved human lung lipidome reveals cellular cooperation in lung function Kyle, Jennifer E.; Clair, Geremy; Bandyopadhyay, Gautam Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-31640-x	journal	September 2018
Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity Min, Chan-Ki; Cheon, Shinhye; Ha, Na-Young Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep25359	journal	May 2016
MPLEx: a method for simultaneous pathogen inactivation and extraction of samples for multi-omics profiling Burnum-Johnson, Kristin E.; Kyle, Jennifer E.; Eisfeld, Amie J. The Analyst, Vol. 142, Issue 3 https://doi.org/10.1039/c6an02486f	journal	January 2017
Potential contribution of alveolar epithelial type I cells to pulmonary fibrosis Kasper, Michael; Barth, Kathrin Bioscience Reports, Vol. 37, Issue 6 https://doi.org/10.1042/BSR20171301	journal	November 2017
A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome Ksiazek, Thomas G.; Erdman, Dean; Goldsmith, Cynthia S. New England Journal of Medicine, Vol. 348, Issue 20, p. 1953-1966 https://doi.org/10.1056/NEJMoa030781	journal	May 2003
Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia Zaki, Ali M.; van Boheemen, Sander; Bestebroer, Theo M. New England Journal of Medicine, Vol. 367, Issue 19 https://doi.org/10.1056/NEJMoa1211721	journal	November 2012
Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques de Wit, E.; Rasmussen, A. L.; Falzarano, D. Proceedings of the National Academy of Sciences, Vol. 110, Issue 41 https://doi.org/10.1073/pnas.1310744110	journal	September 2013
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
Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection Pascal, Kristen E.; Coleman, Christopher M.; Mujica, Alejandro O. Proceedings of the National Academy of Sciences, Vol. 112, Issue 28 https://doi.org/10.1073/pnas.1510830112	journal	June 2015
Link of a ubiquitous human coronavirus to dromedary camels Corman, Victor M.; Eckerle, Isabella; Memish, Ziad A. Proceedings of the National Academy of Sciences, Vol. 113, Issue 35 https://doi.org/10.1073/pnas.1604472113	journal	August 2016
MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape Menachery, Vineet D.; Schäfer, Alexandra; Burnum-Johnson, Kristin E. Proceedings of the National Academy of Sciences, Vol. 115, Issue 5 https://doi.org/10.1073/pnas.1706928115	journal	January 2018
MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity Chu, Daniel K. W.; Hui, Kenrie P. Y.; Perera, Ranawaka A. P. M. Proceedings of the National Academy of Sciences, Vol. 115, Issue 12 https://doi.org/10.1073/pnas.1718769115	journal	March 2018
Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate Wang, Yanjie; Tang, Zan; Huang, Huanwei Proceedings of the National Academy of Sciences, Vol. 115, Issue 10 https://doi.org/10.1073/pnas.1719474115	journal	February 2018
Bayesian Proteoform Modeling Improves Protein Quantification of Global Proteomic Measurements Webb-Robertson, B. -J. M.; Matzke, M. M.; Datta, S. Molecular & Cellular Proteomics https://doi.org/10.1074/mcp.O113.030932	journal	August 2014
Improved quality control processing of peptide-centric LC-MS proteomics data Matzke, Melissa M.; Waters, Katrina M.; Metz, Thomas O. Bioinformatics, Vol. 27, Issue 20 https://doi.org/10.1093/bioinformatics/btr479	journal	August 2011
Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways Chu, Hin; Zhou, Jie; Wong, Bosco Ho-Yin Journal of Infectious Diseases, Vol. 213, Issue 6 https://doi.org/10.1093/infdis/jiv380	journal	July 2015
Middle East Respiratory Syndrome Coronavirus Causes Multiple Organ Damage and Lethal Disease in Mice Transgenic for Human Dipeptidyl Peptidase 4 Li, Kun; Wohlford-Lenane, Christine; Perlman, Stanley Journal of Infectious Diseases, Vol. 213, Issue 5 https://doi.org/10.1093/infdis/jiv499	journal	October 2015
The effective reproductive number of the Omicron variant of SARS-CoV-2 is several times relative to Delta Liu, Ying; Rocklöv, Joacim Journal of Travel Medicine, Vol. 29, Issue 3 https://doi.org/10.1093/jtm/taac037	journal	March 2022
Protein Kinase C-Delta (PKCδ) Tyrosine Phosphorylation is a Critical Regulator of Neutrophil-Endothelial Cell Interaction in Inflammation Soroush, Fariborz; Tang, Yuan; Guglielmo, Kimberly Shock, Vol. 51, Issue 5 https://doi.org/10.1097/SHK.0000000000001247	journal	May 2019
Histopathology of Middle East respiratory syndrome coronovirus (MERS‐CoV) infection – clinicopathological and ultrastructural study Alsaad, Khaled O.; Hajeer, Ali H.; Al Balwi, Mohammed Histopathology, Vol. 72, Issue 3 https://doi.org/10.1111/his.13379	journal	November 2017
Targeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity Chu, Hin; Shuai, Huiping; Hou, Yuxin Science Advances, Vol. 7, Issue 25 https://doi.org/10.1126/sciadv.abf8577	journal	June 2021
Recovery from the Middle East respiratory syndrome is associated with antibody and T cell responses Zhao, Jingxian; Alshukairi, Abeer N.; Baharoon, Salim A. Science Immunology, Vol. 2, Issue 14 https://doi.org/10.1126/sciimmunol.aan5393	journal	August 2017
Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses Sheahan, Timothy P.; Sims, Amy C.; Graham, Rachel L. Science Translational Medicine, Vol. 9, Issue 396 https://doi.org/10.1126/scitranslmed.aal3653	journal	June 2017
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice Sheahan, Timothy P.; Sims, Amy C.; Zhou, Shuntai Science Translational Medicine, Vol. 12, Issue 541 https://doi.org/10.1126/scitranslmed.abb5883	journal	April 2020
A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus Tse, Longping V.; Hou, Yixuan J.; McFadden, Elizabeth Science Translational Medicine, Vol. 15, Issue 715 https://doi.org/10.1126/scitranslmed.adg5567	journal	September 2023
CD8 ⁺ T Cells and Macrophages Regulate Pathogenesis in a Mouse Model of Middle East Respiratory Syndrome Coleman, Christopher M.; Sisk, Jeanne M.; Halasz, Gabor Journal of Virology, Vol. 91, Issue 1 https://doi.org/10.1128/JVI.01825-16	journal	January 2017
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
Differential Expression of the Middle East Respiratory Syndrome Coronavirus Receptor in the Upper Respiratory Tracts of Humans and Dromedary Camels Widagdo, W.; Raj, V. Stalin; Schipper, Debby Journal of Virology, Vol. 90, Issue 9 https://doi.org/10.1128/JVI.02994-15	journal	May 2016
Glycosylation of Mouse DPP4 Plays a Role in Inhibiting Middle East Respiratory Syndrome Coronavirus Infection Peck, Kayla M.; Cockrell, Adam S.; Yount, Boyd L. Journal of Virology, Vol. 89, Issue 8 https://doi.org/10.1128/JVI.03445-14	journal	April 2015
Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak Kim, Yuri; Cheon, Shinhye; Min, Chan-Ki mBio, Vol. 7, Issue 2 https://doi.org/10.1128/mBio.00019-16	journal	May 2016
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
Unfolded Protein Response Inhibition Reduces Middle East Respiratory Syndrome Coronavirus-Induced Acute Lung Injury Sims, Amy C.; Mitchell, Hugh D.; Gralinski, Lisa E. mBio, Vol. 12, Issue 4 https://doi.org/10.1128/mBio.01572-21	journal	August 2021
Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis Gralinski, Lisa E.; Sheahan, Timothy P.; Morrison, Thomas E. mBio, Vol. 9, Issue 5 https://doi.org/10.1128/mBio.01753-18	journal	October 2018
High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia Alshukairi, Abeer N.; Zheng, Jian; Zhao, Jingxian mBio, Vol. 9, Issue 5 https://doi.org/10.1128/mBio.01985-18	journal	November 2018
MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses Nakayasu, Ernesto S.; Nicora, Carrie D.; Sims, Amy C. mSystems, Vol. 1, Issue 3 https://doi.org/10.1128/mSystems.00043-16	journal	May 2016
Emerging Human Middle East Respiratory Syndrome Coronavirus Causes Widespread Infection and Alveolar Damage in Human Lungs Hocke, Andreas C.; Becher, Anne; Knepper, Jessica American Journal of Respiratory and Critical Care Medicine, Vol. 188, Issue 7 https://doi.org/10.1164/rccm.201305-0954LE	journal	October 2013
Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways Okuda, Kenichi; Chen, Gang; Subramani, Durai B. American Journal of Respiratory and Critical Care Medicine, Vol. 199, Issue 6 https://doi.org/10.1164/rccm.201804-0734OC	journal	March 2019
An Official American Thoracic Society Workshop Report: Features and Measurements of Experimental Acute Lung Injury in Animals Matute-Bello, Gustavo; Downey, Gregory; Moore, Bethany B. American Journal of Respiratory Cell and Molecular Biology, Vol. 44, Issue 5 https://doi.org/10.1165/rcmb.2009-0210ST	journal	May 2011
IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes Channappanavar, Rudragouda; Fehr, Anthony R.; Zheng, Jian Journal of Clinical Investigation, Vol. 129, Issue 9 https://doi.org/10.1172/JCI126363	journal	July 2019
Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection Schmidt, Megan E.; Knudson, Cory J.; Hartwig, Stacey M. PLOS Pathogens, Vol. 14, Issue 1 https://doi.org/10.1371/journal.ppat.1006810	journal	January 2018
A human coronavirus evolves antigenically to escape antibody immunity Eguia, Rachel T.; Crawford, Katharine H. D.; Stevens-Ayers, Terry PLOS Pathogens, Vol. 17, Issue 4 https://doi.org/10.1371/journal.ppat.1009453	journal	April 2021
The 1-Year Impact of Severe Acute Respiratory Syndrome on Pulmonary Function, Exercise Capacity, and Quality of Life in a Cohort of Survivors Hui, David S.; Wong, Ka T.; Ko, Fanny W. Chest, Vol. 128, Issue 4 https://doi.org/10.1378/chest.128.4.2247	journal	October 2005
Correlation between Pneumonia Severity and Pulmonary Complications in Middle East Respiratory Syndrome Park, Wan Beom; Jun, Kang Il; Kim, Gayeon Journal of Korean Medical Science, Vol. 33, Issue 24 https://doi.org/10.3346/jkms.2018.33.e169	journal	January 2018
Pathogenicity and Viral Shedding of MERS-CoV in Immunocompromised Rhesus Macaques Prescott, Joseph; Falzarano, Darryl; de Wit, Emmie Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.00205	journal	February 2018
Clinical Presentation and Outcomes of Middle East Respiratory Syndrome in the Republic of Korea Choi, Won Suk; Kang, Cheol-In; Kim, Yonjae Infection & Chemotherapy, Vol. 48, Issue 2 https://doi.org/10.3947/ic.2016.48.2.118	journal	January 2016
Leptin Receptor Deficiency Impairs Lymph Node Development and Adaptive Immune Response Cardani-Boulton, Amber; Sung, Sun-Sang J.; Petri, William A. The Journal of Immunology, Vol. 212, Issue 6 https://doi.org/10.4049/jimmunol.2100985	journal	January 2024
Follow-up chest radiographic findings in patients with MERS-CoV after recovery Das, Karuna M.; Lee, Edward Y.; Singh, Rajvir Indian Journal of Radiology and Imaging, Vol. 27, Issue 03 https://doi.org/10.4103/ijri.IJRI_469_16	journal	July 2017

Similar Records

A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2

Journal Article · Mon Mar 22 00:00:00 UTC 2021 · PLoS Biology (Online) · OSTI ID:1815799

Kim, Kwang Su; Ejima, Keisuke; Iwanami, Shoya; +11 more

Omics Lethal Human Viruses Project Profiling of the Host Response to MERS-CoV Infection, Processed Experimental Dataset Catalog

Dataset · Mon Jan 18 04:00:00 UTC 2021 · OSTI ID:1813911

Anderson, Lindsey N.; Eisfeld, Amie J.; Waters, Katrina M.

A Network Integration Approach to Predict Conserved Regulators Related to Pathogenicity of Influenza and SARS-CoV Respiratory Viruses

Journal Article · Thu Jul 25 04:00:00 UTC 2013 · PLoS One, 8(7):e69374 · OSTI ID:1090172

Mitchell, Hugh D.; Eisfeld, Amie J.; Sims, Amy; +21 more

Related Subjects

MERS-CoV
SARS-CoV-2
coronavirus
genomics
lung infection
proteomics
viral pathogenesis

Title: Dysregulation of lung epithelial cell homeostasis and immunity contributes to Middle East respiratory syndrome coronavirus disease severity

Citation Formats

References (70)

Similar Records

Related Subjects