Human Betacoronavirus 2c EMC/2012–related Viruses in Bats, Ghana and Europe

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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.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 . The dromedary camel (Camelus dromedarius) has been shown to be the reservoir host for primary human infections 2-8 , although other susceptible animals 9-11 , including bats 12,13 , are suspected also to be hosts for this virus. MERS-like-CoVs have been sequenced from bat samples, mainly from insectivorous bats, but they have not yet been successfully isolated [14][15][16][17][18][19][20][21] . Screening of over 5000 insectivorous bats from Ghana, Ukraine, Romania, Germany, and the Netherlands showed that MERS-CoV-like viruses were detected in 24.9% of Nycteris bats and 14.7% of Pipistrelle bats 17 .MERS-CoV uses dipeptidyl peptidase-4 (DPP4) as its receptor to infect its target cells, including bat cells 22 . 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-CoV 12,21,23 . MERS-like-CoVs probably also use DPP4 as indicated by studies on the Tylonycteris bat CoV HKU4, one of the MERS-like-CoVs 21 . HKU4 uses DPP4 to infect both bat and human cells in vitro 24,25 . It is known that DPP4 is differently distributed in the respiratory tract of humans and other susceptible livestock animals, including dromedary camels 9,26 . DPP4 expression in the nasal epithelium of the camel, llama, and pig allows them to develop upper respiratory tract infection upon intranasal inoculation with MERS-CoV 2,9,26 , while in humans, DPP4 is exclusively expressed in the lower respiratory tract epithelium,...