While a number of human coronaviruses are believed to be originated from ancestral viruses in bats, it remains unclear if bat coronaviruses are ready to cause direct bat-to-human transmission. Here, we report the isolation of a MERS-related coronavirus, Tylonycteris -bat-CoV-HKU4, from lesser bamboo bats. Tylonycteris -bat-CoV-HKU4 replicates efficiently in human colorectal adenocarcinoma and hepatocarcinoma cells with cytopathic effects, and can utilize human-dipeptidyl-peptidase-4 and dromedary camel-dipeptidyl-peptidase-4 as the receptors for cell entry. Flow cytometry, co-immunoprecipitation and surface plasmon resonance assays show that Tylonycteris -bat-CoV-HKU4-receptor-binding-domain can bind human-dipeptidyl-peptidase-4, dromedary camel-dipeptidyl-peptidase-4, and Tylonycteris pachypus- dipeptidyl-peptidase-4. Tylonycteris -bat-CoV-HKU4 can infect human-dipeptidyl-peptidase-4-transgenic mice by intranasal inoculation with self-limiting disease. Positive virus and inflammatory changes were detected in lungs and brains of infected mice, associated with suppression of antiviral cytokines and activation of proinflammatory cytokines and chemokines. The results suggest that MERS-related bat coronaviruses may overcome species barrier by utilizing dipeptidyl-peptidase-4 and potentially emerge in humans by direct bat-to-human transmission. Several human coronaviruses (CoV) have been proposed to emerge from bats but evidence of direct bat-to-human transmission is slim. In this work, the authors isolate a MERS-related CoV strain directly from bats and show that it infects target cells in vitro and engineered mice through the human DDP4 receptor.
【저자키워드】 viral pathogenesis, Viral reservoirs, 【초록키워드】 coronavirus, Human, lung, Transmission, chemokines, in vitro, virus, Brain, mice, Isolation, CoV, bat, receptor, bats, intranasal, Evidence, Cytometry, Flow, target cell, Proinflammatory cytokine, Activation, cell entry, cytopathic effects, co-immunoprecipitation, while, Tylonycteris, infect, Cell, DDP4, self-limiting disease, human coronavirus, replicate, overcome, bat coronavirus, antiviral cytokine, inflammatory change, 【제목키워드】 coronavirus, DPP4, mice, bat, infect,