Middle East respiratory syndrome

Alimuddin Zumla, David S Hui, Stanley Perlman, Alimuddin Zumla, David S Hui, Stanley Perlman

Abstract

Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a novel single-stranded, positive-sense RNA betacoronavirus (MERS-CoV). Dromedary camels, hosts for MERS-CoV, are implicated in direct or indirect transmission to human beings, although the exact mode of transmission is unknown. The virus was first isolated from a patient who died from a severe respiratory illness in June, 2012, in Jeddah, Saudi Arabia. As of May 31, 2015, 1180 laboratory-confirmed cases (483 deaths; 40% mortality) have been reported to WHO. Both community-acquired and hospital-acquired cases have been reported with little human-to-human transmission reported in the community. Although most cases of MERS have occurred in Saudi Arabia and the United Arab Emirates, cases have been reported in Europe, the USA, and Asia in people who travelled from the Middle East or their contacts. Clinical features of MERS range from asymptomatic or mild disease to acute respiratory distress syndrome and multiorgan failure resulting in death, especially in individuals with underlying comorbidities. No specific drug treatment exists for MERS and infection prevention and control measures are crucial to prevent spread in health-care facilities. MERS-CoV continues to be an endemic, low-level public health threat. However, the virus could mutate to have increased interhuman transmissibility, increasing its pandemic potential.

Copyright © 2015 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
Global MERS cases (A) Confirmed cases of MERS as of May 31, 2015, by date (n=1180). (B) Location of MERS deaths/cases, as of May 31, 2015 (n=1180). Shows countries in which patients were identified. Data from WHO and Promed Mail. MERS=Middle East respiratory syndrome.
Figure 2
Figure 2
MERS-CoV virion, replication strategy, and genomic structure (A) Electron micrograph of MERS-CoV virions in large single membrane vesicles and in the periphery of the cell. Virion spikes are visible as is the electron-dense core consisting of the RNA genome encapsidated in the N protein. Provided by Montserrat Barcena, Ronald Limpens and Eric Snijder (Leiden University Medical Center, Netherlands). (B) MERS-CoV, showing viral RNA structural proteins spike (S), envelope (E), matrix (M), and nucleocapsid (N). (C) Human airway cells infected with MERS-CoV and assessed for viral antigen by indirect immunofluorescence assay with an anti-MERS-CoV N antibody. Green shows MERS-CoV-positive cells, blue shows nuclear stain. A similar assay is used for serological diagnosis of MERS. Provided by Christine Wohlford-Lenane (University of Iowa, Iowa City, IA). (D) Virus life-cycle. (E) The MERS-CoV genome consists of 11 ORFs that code for the virus replication machinery (ORF 1a and ORF 1b) and the major structural proteins: spike (S), envelope (E), matrix (M), and nucleocapsid (N). ORF 1b, produced by a–1 basepair frameshift from ORF 1a, encodes the RNA-dependent RNA polymerase (nsp12), helicase (nsp13), N7-methyltransferase (nsp14), a 3'–5' exonuclease for RNA proofreading (nsp14), 2'-O-methyltransferase (nsp16), and an endonuclease specific for U and found only in nidoviruses (nsp15). MERS-CoV also encodes five accessory proteins in the 3' end of the genome (3a/b, 4, 5, 8b), which share no homology with proteins from host cells or other viruses, including coronaviruses. 4a and 4b are interferon antagonists, but the functions of the other accessory proteins are unknown.
Figure 3
Figure 3
Ecology and transmission of MERS-CoV MERS-CoV might have originally spread from bats to camels and other, as yet unidentified, intermediate hosts. The virus has circulated in camel populations in Africa and the Arabian peninsula for at least 20 years. In 2012, MERS-CoV spread to human populations, with camels the most likely source. Several possible routes of spread from camels to humans exist. MERS-CoV is believed to be transmitted among human beings by droplet, contact, and perhaps airborne spread. MERS manifests in people in various ways, ranging from asymptomatic to fulminant infections. Patients with underlying disease such as diabetes or kidney or liver disease or who are immunocompromised develop more severe disease and have a higher mortality rate after infection. Image credits: camel birthing from Noboru Komine/Science Photo Library, camel milking from ACEI Cheung/CC BY-SA 2.0, camel owner contact from Peter Menzel/Science Photo Library, MERS virus from AMI Images/Science Photo Library. MERS-CoV=Middle East respiratory syndrome coronavirus.

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