The emergence of the Middle East respiratory syndrome coronavirus

Abstract

On September 20, 2012, a Saudi Arabian physician reported the isolation of a novel coronavirus from a patient with pneumonia on ProMED-mail. Within a few days, the same virus was detected in a Qatari patient receiving intensive care in a London hospital, a situation reminiscent of the role air travel played in the spread of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. SARS-CoV originated in China's Guangdong Province and affected more than 8000 patients in 26 countries before it was contained 6 months later. Over a year after the emergence of this novel coronavirus--Middle East respiratory syndrome coronavirus (MERS-CoV)--it has caused 178 laboratory-confirmed cases and 76 deaths. The emergence of a second highly pathogenic coronavirus within a decade highlights the importance of a coordinated global response incorporating reservoir surveillance, high-containment capacity with fundamental and applied research programs, and dependable communication pathways to ensure outbreak containment. Here, we review the current state of knowledge on the epidemiology, ecology, molecular biology, clinical features, and intervention strategies of the novel coronavirus, MERS-CoV.

Keywords: MERS-CoV; coronavirus; epidemiology; intervention strategies; molecular biology.

Figure 1

False‐color MERS‐CoV particle visualized by electron microscopy. A MERS‐CoV particle (yellow) attached to the surface of a cell (red). The characteristic MERS‐CoV spike glycoproteins are clearly visible on the surface of the MERS‐CoV particle.

Figure 2

Geographic distribution of the MERS‐CoV outbreak. The geographic distribution of MERS‐CoV cases up to February 1, 2014 is shown. Travel history of cases imported outside of the Arabian Peninsula is indicated with dotted arrows. Countries with primary MERS‐CoV cases are shown in brown, countries with imported MERS‐CoV cases and no confirmed human‐to‐human transmission are shown in pink, and countries with imported MERS‐CoV cases and subsequent human‐to‐human transmission are shown in green.

Figure 3

Timeline of the MERS‐CoV outbreak. Temporal distribution of MERS‐CoV cases from March 2012 through December 2013. Significant outbreak events and scientific advances during this time period are highlighted below.

Figure 4

Coronavirus phylogeny. Phylogenetic tree of coronaviruses with representatives of each of the four genera; Alpha (pink), Beta (gray), Delta (blue), and Gammacoronavirus (yellow). Betacoronaviruses are further subdivided into clades A through D, with clade B (green) containing SARS‐CoV and clade C (orange) containing MERS‐CoV. All known human coronaviruses are represented in red. Maximum‐likelihood trees were generated with the MEGA5 software package using a 1231‐nucleotide segment within the RdRp. Trees were visualized using Figtree. Bootstrap values above 75 are shown. CoV isolation origin abbreviations as follows: H: human; Bt: bat; BtSL: bat SARS‐like; BW: beluga whale; IBV: chicken; FIPV: feline; TGEV: swine; M: mink; MHV: murine; Th: thrush; Bu: bulbul; Mun: munia.

Figure 5

Putative MERS‐CoV transmission cycle. The putative transmission cycle for MERS‐CoV. MERS‐CoV likely originated from bats, acting as the natural reservoir. From the natural reservoir, MERS‐CoV spilled either directly over to humans (green arrow) or via an intermediate host (dromedary camels, purple arrow). Currently, the exact route of zoonotic transmission of MERS‐CoV into the human population remains unknown although the presence of MERS‐CoV neutralizing antibodies and the detection of MERS‐CoV in dromedary camels suggest that this species is likely to play a major role in the emergence of MERS‐CoV. Phylogenetic analysis suggests that multiple introductions of MERS‐CoV into the human population have occurred and both zoonotic transmission events and human‐to‐human transmission (blue arrows) drive the current MERS‐CoV outbreak.

Figure 6

MERS‐CoV spike glycoprotein and DPP4 receptor interaction. (a) The linear organization of the S1 subunit of MERS‐CoV spike glycoprotein with the variable RBD located at amino acid residues 367–607, with a RBM containing the critical amino acid residues for binding at residues 484–567. (b) The crystal structure of the MERS‐CoV RBD coupled with the receptor dipeptidyl peptidase IV (DPP4). DPP4 is structurally divided into an alpha‐ and beta‐hydrolase domain, and a beta‐propeller domain. The beta‐propeller domain of DPP4 (pink) interacts with the RBM region (light blue) of the MERS‐CoV spike protein RBD. The schematic representation of the DPP4 – MERS‐CoV spike protein RBD structure was generated using chimera and protein accession number 4KR0 (Lu et al., 2013).

Figure 7

Geographic distribution of dromedary camels. The global distribution of dromedary camels is indicated by yellow shading (Mukasa‐Mugerwa, 1981).