Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.
Highlights
In 2012, a novel human coronavirus causing frequently fatal disease emerged in Western Asia [1] and was named ‘‘Middle East respiratory syndrome coronavirus (MERS-CoV)’’ [2]
As bats could be a potential reservoir for MERS-CoV, we tested the susceptibility of ten diverse bat cells lines to infection with MERS-CoV/EMC or MERS-CoV/Jor at an multiplicity of infection (MOI) of 1
PESUB5L, R05T, R06E, and Tb1Lu cell lines did not support productive MERS-CoV virus infection (Figure 1A, 1B). These results were confirmed by immunofluorescence assay (IFA) in cell lines inoculated with MERS-CoV/EMC (Figure 1C) or MERS-CoV/Jor (Figure 1D)
Summary
In 2012, a novel human coronavirus causing frequently fatal disease emerged in Western Asia [1] and was named ‘‘Middle East respiratory syndrome coronavirus (MERS-CoV)’’ [2]. Increasing evidence points to dromedaries (Camelus dromedarius) as an intermediate reservoir contributing to the emergence of Middle East respiratory syndrome (MERS) in humans. Coronaviral genomes detected in nasal swabs obtained from dromedaries proved to be identical to genomes of human MERS-CoV isolates [4,5,9]. One such genome was detected in a patient who had been caring for a sick dromedary and directly from that animal [10]. MERS-CoV was directly isolated from a dromedary in Qatar [11]
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