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      Molecular Pathogenesis of Middle East Respiratory Syndrome (MERS) Coronavirus

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          Abstract

          Purpose of Review

          Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is listed in the World Health Organization’s blueprint of priority diseases that need immediate research. Camels are reservoirs of this virus, and the virus spills over into humans through direct contact with camels. Human-to-human transmission and travel-associated cases have been identified as well. Limited studies have characterized the molecular pathogenesis of MERS-CoV. Most studies have used ectopic expression of viral proteins to characterize MERS-CoV and its ability to modulate antiviral responses in human cells. Studies with live virus are limited, largely due to the requirement of high containment laboratories. In this review, we have summarized current studies on MERS-CoV molecular pathogenesis and have mentioned some recent strategies that are being developed to control MERS-CoV infection.

          Recent Findings

          Multiple antiviral molecules with the potential to inhibit MERS-CoV infection by disrupting virus-receptor interactions are being developed and tested. Although human vaccine candidates are still being developed, a candidate camel vaccine is being tested for efficacy. Combination of supportive treatment with interferon and antivirals is also being explored.

          Summary

          New antiviral molecules that inhibit MERS-CoV and host cell receptor interaction may become available in the future. Additional studies are required to identify and characterize the pathogenesis of MERS-CoV EMC/2012 and other circulating strains. An effective MERS-CoV vaccine, for humans and/or camels, along with an efficient combination antiviral therapy may help us prevent future MERS cases.

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          Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats.

          S K P Lau, P Woo, K. S. M. Li … (2005)
          Although the finding of severe acute respiratory syndrome coronavirus (SARS-CoV) in caged palm civets from live animal markets in China has provided evidence for interspecies transmission in the genesis of the SARS epidemic, subsequent studies suggested that the civet may have served only as an amplification host for SARS-CoV. In a surveillance study for CoV in noncaged animals from the wild areas of the Hong Kong Special Administration Region, we identified a CoV closely related to SARS-CoV (bat-SARS-CoV) from 23 (39%) of 59 anal swabs of wild Chinese horseshoe bats (Rhinolophus sinicus) by using RT-PCR. Sequencing and analysis of three bat-SARS-CoV genomes from samples collected at different dates showed that bat-SARS-CoV is closely related to SARS-CoV from humans and civets. Phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b CoV, distantly related to known group 2 CoV. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike genes, ORF 3 and ORF 8, which are the regions where most variations also were observed between human and civet SARS-CoV genomes. In addition, the presence of a 29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats by using an enzyme immunoassay. Neutralizing antibody to human SARS-CoV also was detected in bats with lower viral loads. Precautions should be exercised in the handling of these animals.
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            Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus

            Abdullah Assiri, Allison McGeer, Trish M. Perl … (2013)
            In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care-acquired MERS-CoV infections. Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases). Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.
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              Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014

              Dianna Ng, Farida Al Hosani, M Kelly Keating … (2016)
              Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti–MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans.
              Article 0 comments Cited 240 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Karen Mossman: mossk@mcmaster.ca
                Journal
                Journal ID (nlm-ta): Curr Clin Microbiol Rep
                Journal ID (iso-abbrev): Curr Clin Microbiol Rep
                Title: Current Clinical Microbiology Reports
                Publisher: Springer International Publishing (Cham )
                ISSN (Electronic): 2196-5471
                Publication date (Electronic): 5 July 2019
                Publication date (Print): 2019
                Volume: 6
                Issue: 3
                Pages: 139-147
                Affiliations
                [1 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, Michael DeGroote Institute for Infectious Disease Research, , McMaster University, ; Hamilton, Ontario L8S 4L8 Canada
                [2 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Biochemistry and Biomedical Sciences, McMaster Immunology Research Center, Michael DeGroote Institute for Infectious Disease Research, , McMaster University, ; Hamilton, Ontario L8S 4L8 Canada
                Article
                Publisher ID: 122
                DOI: 10.1007/s40588-019-00122-7
                PMC ID: 7100557
                SO-VID: e5378c4b-827e-4c7e-9c94-8526fa5f01d6
                Copyright © © Springer Nature Switzerland AG 2019
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Categories
                Subject: Virology (A Nicola, Section Editor)
                Custom metadata
                issue-copyright-statement © Springer Nature Switzerland AG 2019

                Keywords: mers,coronavirus,pathogenesis,therapeutics
                Data availability:
                Keywords: mers, coronavirus, pathogenesis, therapeutics

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