Pathogenesis of Middle East respiratory syndrome coronavirus

Abstract

Human coronaviruses (CoVs) mostly cause a common cold that is mild and self-limiting. Zoonotic transmission of CoVs such as the recently identified Middle East respiratory syndrome (MERS)-CoV and severe acute respiratory syndrome (SARS)-CoV, on the other hand, may be associated with severe lower respiratory tract infection. This article reviews the clinical and pathological data available on MERS and compares it to SARS. Most importantly, chest radiographs and imaging results of patients with MERS show features that resemble the findings of organizing pneumonia, different from the lesions in SARS patients, which show fibrocellular intra-alveolar organization with a bronchiolitis obliterans organizing pneumonia-like pattern. These findings are in line with differences in the induction of cytopathological changes, induction of host gene responses and sensitivity to the antiviral effect of interferons in vitro when comparing both MERS-CoV and SARS-CoV. The challenge will be to translate these findings into an integrated picture of MERS pathogenesis in humans and to develop intervention strategies that will eventually allow the effective control of this newly emerging infectious disease.

Keywords: MERS; SARS; coronavirus; respiratory tract; virology.

Figure 1

Schematic diagram of a MERS‐CoV particle and MERS‐CoV genome organization: S, spike protein; M, membrane protein, E, envelope protein; N, nucleocapsid protein.

Figure 2

Zoonotic transmission of MERS‐CoV. The emergence of MERS‐CoV from dromedary camels is facilitated by the presence of a highly similar viral receptor (DPP4) in humans. Hypothetically, MERS‐CoV present in dromedary camels may have emerged from CoVs in bats that also use DPP4 as an entry receptor

Figure 3

Histopathology and in situ detection of MERS‐CoV in the lungs of a cynomolgus macaque after intratracheal inoculation with MERS‐CoV. (A) The alveolar septa are mildly thickened, with infiltration of a few neutrophils and monocytes. There are also increased numbers of intraluminal alveolar macrophages and a few neutrophils; H&E, magnification = ×10. (B). MERS‐CoV specific RNA by in situ hybridization (ISH), targeting the MERS‐CoV nucleocapsid, is present in lung tissue of of a cynomolgus macaque after intratracheal inoculation with MERS‐CoV. RNA is present predominantly in type II alveolar epithelial cells, with less in type I epithelial cells; ISH, magnification = ×10.