Middle East respiratory syndrome–related coronavirus (MERS-CoV, Betacoronavirus cameli) or EMC/2012 (HCoV-EMC/2012), is the virus that causes Middle East respiratory syndrome (MERS). It is a species of coronavirus which infects humans, bats, and camels. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the DPP4 receptor. The species is a member of the genus Betacoronavirus and subgenus Merbecovirus. Initially called simply novel coronavirus or nCoV, with the provisional names 2012 novel coronavirus (2012-nCoV) and human coronavirus 2012 (HCoV-12 or hCoV-12), it was first reported in June 2012 after genome sequencing of a virus isolated from sputum samples from a person who fell ill in a 2012 outbreak of a new flu-like respiratory illness. By July 2015, MERS-CoV cases had been reported in over 21 countries, in Europe, North America and Asia as well as the Middle East. MERS-CoV is one of several viruses identified by the World Health Organization (WHO) as a likely cause of a future epidemic. They list it for urgent research and development. In 2022, a new MERS-related Coronavirus, NeoCoV, was identified in bats, which was found to pose a potential pandemic risk.
Virology The virus MERS-CoV is a member of the beta group of coronavirus, Betacoronavirus, lineage C. MERS-CoV genomes are phylogenetically classified into two clades, clade A and B. The earliest cases were of clade A clusters, while the majority of more recent cases are of the genetically distinct clade B. MERS-CoV is one of seven known coronaviruses to infect humans, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, the original SARS-CoV (or SARS-CoV-1), and SARS-CoV-2. It has frequently been referred to as a SARS-like virus. By November, 2019, 2,494 cases of MERS had been reported with 858 deaths, implying a case fatality rate of greater than 30%.
Early cases and spillover event The first confirmed case was reported in Jeddah, Saudi Arabia in June 2012. Egyptian virologist Ali Mohamed Zaki isolated and identified a previously unknown coronavirus from the man's lungs. Zaki then posted his findings on 24 September 2012 on ProMED-mail. Cells inoculated with the isolated virus showed cytopathic effects (CPE), in the form of rounding and syncytia formation. A second case was found in September 2012, when a 49-year-old man living in Qatar presented with similar flu symptoms. A sequence of the virus was nearly identical to that of the first case. Among animal reservoirs, CoV has a large genetic diversity yet the samples from patients suggested a similar genome, and therefore common source, though the data were limited. It was determined through molecular clock analysis that viruses from the EMC/2012 and England/Qatar/2012 date to early 2011, suggesting that these cases were descended from a single zoonotic event. It appeared the MERS-CoV had been circulating in the human population for more than a year without detection, and suggested independent transmission from an unknown source.
Tropism In humans, the virus has a strong tropism for nonciliated bronchial epithelial cells, and it has been shown to effectively evade the innate immune responses and antagonize interferon (IFN) production in these cells. This tropism is unique in that most respiratory viruses target ciliated cells. Due to the clinical similarity between MERS-CoV and SARS-CoV-1, it was proposed that they may use the same cellular receptor; the exopeptidase, angiotensin converting enzyme 2 (ACE2). However, it was later discovered that neutralization of ACE2 by recombinant antibodies does not prevent MERS-CoV infection. Further research identified dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional cellular receptor for MERS-CoV. Unlike other known coronavirus receptors, the enzymatic activity of DPP4 is not required for infection. As would be expected, the amino acid sequence of DPP4 is highly conserved across species and is expressed in the human bronchial epithelium and kidneys. Bat DPP4 genes appear to have been subject to a high degree of adaptive evolution as a response to coronavirus infections, so the lineage leading to MERS-CoV may have circulated in bat populations for a long period of time before being transmitted to people.
Transmission
On 13 February 2013, the World Health Organization stated that "the risk of sustained person-to-person transmission appears to be very low." The cells MERS-CoV infects in the lungs only account for 20% of respiratory epithelial cells, so a large number of virions are likely needed to be inhaled to cause infection. Anthony Fauci of the National Institutes of Health in Bethesda, Maryland, stated that MERS-CoV "does not spread in a sustained person to person way at all," while noting the possibility that the virus could mutate into a strain that does transmit from person to person. However, the infection of healthcare workers has led to concerns of human to human transmission. The Centers for Disease Control and Prevention (CDC) list MERS as transmissible from human to human. They state that "MERS-CoV has been shown to spread between people who are in close contact. Transmission from infected patients to healthcare personnel has also been observed. Clusters of cases in several countries are being investigated." However, on the 28th of May, the CDC revealed that the Illinois man who was originally thought to have been the first incidence of person-to-person spread (from the Indiana man at a business meeting), had in fact tested negative for MERS-CoV. After completing additional and more definitive tests using a neutralising antibody assay, experts at the CDC concluded that the Indiana patient did not spread the virus to the Illinois patient. Tests concluded that the Illinois man had not been previously infected. It is possible for MERS to be symptomless, and early research has shown that up to 20% of cases show no signs of active infection but have MERS-CoV antibodies in their blood.
Evolution
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