Host Determinants of MERS-CoV Transmission and Pathogenesis

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. In dromedary camels, the virus only causes a mild infection but it spreads efficiently between animals. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. One of these host factors, the MERS-CoV receptor dipeptidyl peptidase-4 (DPP4), may be a critical determinant because it is variably expressed in MERS-CoV-susceptible species as well as in humans. This could partially explain inter- and intraspecies differences in the tropism, pathogenesis, and transmissibility of MERS-CoV. In this review, we explore the role of DPP4 and other host factors in MERS-CoV transmission and pathogenesis-such as sialic acids, host proteases, and interferons. Further characterization of these host determinants may potentially offer novel insights to develop intervention strategies to tackle ongoing outbreaks.

Keywords: DPP4; MERS-CoV; host factors; pathogenesis; transmission.

Figure 1

Schematic figure depicting four structural proteins of Middle East respiratory syndrome coronavirus (MERS-CoV), i.e., S, E, M, and N proteins (A); a cartoon representation of MERS-CoV S1 protein binding to DPP4 (PDB code 4L72) (B). The S protein consists of the S1 and S2 subunits. The α/β hydrolase domain of DPP4 is indicated in red, β-propeller domain in green, while part of the MERS-CoV S1 protein is shown in blue.

Figure 2

Schematic overview of viral RNA and infectious virus shedding of MERS-CoV-inoculated dromedary camels, pigs, and rabbits. Each data point represents the average data from previous experiments [17,33,84]. Viral RNA is measured in TCID₅₀/mL genome equivalents, while infectious virus is expressed in TCID₅₀/mL.

Figure 3

Schematic representation of DPP4 expression and MERS-CoV-recognized α2,3-sialic acid glycotopes in the respiratory tract of dromedary camel, pig, rabbit, human, and sheep.

Figure 4

MERS-CoV infection in the lungs of asymptomatic-to-mild (left panel) and severe-to-fatal cases (right panel). Shown is a hypothetical model with two critical host determinants, DPP4 and interferon, differentially expressed in asymptomatic-to-mild and severe-to-fatal MERS-CoV infection.