Tissue Distribution of the MERS-Coronavirus Receptor in Bats

W Widagdo,Judith M A Van Den Brand,Debby Schipper,Lineke Begeman,Bart L Haagmans,Chantal B Reusken,Peter R Van Run,Andrew A Cunningham,Nils Kley

doi:10.1038/s41598-017-01290-6

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor. The distribution of DPP4 in the respiratory tract tissues of humans and camels reflects MERS-CoV tropism. Apart from dromedary camels, insectivorous bats are suggested as another natural reservoir for MERS-like-CoVs. In order to gain insight on the tropism of these viruses in bats, we studied the DPP4 distribution in the respiratory and extra-respiratory tissues of two frugivorous bat species (Epomophorus gambianus and Rousettus aegyptiacus) and two insectivorous bat species (Pipistrellus pipistrellus and Eptesicus serotinus). In the frugivorous bats, DPP4 was present in epithelial cells of both the respiratory and the intestinal tract, similar to what has been reported for camels and humans. In the insectivorous bats, however, DPP4 expression in epithelial cells of the respiratory tract was almost absent. The preferential expression of DPP4 in the intestinal tract of insectivorous bats, suggests that transmission of MERS-like-CoVs mainly occurs via the fecal-oral route. Our results highlight differences in the distribution of DPP4 expression among MERS-CoV susceptible species, which might influence variability in virus tropism, pathogenesis and transmission route.

Highlights

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in the human population in 2012 and has been causing multiple outbreaks of human disease, mainly in the Arabian Peninsula[1]
Immunohistochemistry to detect dipeptidyl peptidase-4 (DPP4) was performed on nose, lung, intestine, kidney, salivary gland, and liver tissues of different bat species: common pipistrelle bat, serotine bat, Gambian epauletted fruit bat, and Egyptian fruit bat
We show that DPP4 is differentially expressed among bat species, especially between insectivorous and frugivorous bats

Summary

Introduction

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in the human population in 2012 and has been causing multiple outbreaks of human disease, mainly in the Arabian Peninsula[1]. Analysis of DPP4 sequences from different bat species and in-vitro infection studies with various bat cell lines suggested that multiple bat species are susceptible to MERS-CoV12,21,23. It is known that DPP4 is differently distributed in the respiratory tract of humans and other susceptible livestock animals, including dromedary camels[9,26]. The absence of DPP4 expression in the upper respiratory tract epithelium of sheep renders this tissue to be non-susceptible in-vivo[9]. These data indicate that the localization of DPP4 expression in tissues reflects MERS-CoV susceptibility and tropism in vivo. Our study aimed to understand the tropism of MERS-like-CoVs in bats by mapping the distribution of DPP4 expression in tissues from four bat species. We show that DPP4 localization varies among MERS-CoV susceptible species[9,26] and between bat species, which may imply variability in MERS-like-CoVs tropism, pathogenesis, and transmission route

Methods

Results

Conclusion