Kenyan bat coronavirus uses human CEACAM6 to enter cells, raising spillover concerns An international team of researchers has identified an East African bat coronavirus capable of entering human cells through the human protein CEACAM6, a receptor widely expressed in the lung. The discovery, published in Nature, highlights a potential zoonotic threat while current field evidence shows no significant spillover into human populations. Scientists from the University of York, the University of Cambridge, the Pirbright Institute, the KEMRI-Wellcome Trust Research Programme, and the National Museums of Kenya collaborated on the study. Rather than working with live viruses, researchers used genetic sequences from GenBank to synthesize spike proteins from 27 bat-derived alphacoronaviruses. These were screened against a library of human coronavirus receptors. The spike protein of Cardioderma cor coronavirus KY43 (CcCoV-KY43), isolated from the heart-nosed bat in Kenya, was found to bind directly to human CEACAM6. Structural analysis confirmed that the virus’s receptor-binding domain interacts with the amino-terminal IgV-like domain of CEACAM6. Overexpression of CEACAM6 in previously non-permissive human cells enabled viral entry, demonstrating its functional role as a receptor. CEACAM6 is naturally expressed in human epithelial cells, particularly in the respiratory tract, and is known to be overexpressed in certain cancers. While this raises concerns about potential pathogenic mechanisms should spillover occur, the study found no serological evidence of recent infection in individuals from the Taveta region of Kenya, where the virus was detected. Further characterization revealed that two additional alphacoronaviruses from the same geographic region as well use human CEACAM6 for cell entry. In contrast, related viruses from Rhinolophus bats in Russia and China showed more restricted tropism for nonhuman CEACAM6 variants, suggesting geographic variation in receptor usage among alphacoronaviruses. The researchers emphasize that identifying alternative viral entry mechanisms like CEACAM6 use is critical for pandemic preparedness. By expanding the map of potential zoonotic pathways, such studies improve early detection capabilities and inform surveillance strategies for emerging threats. Whereas CcCoV-KY43 has not demonstrated the ability to infect humans in natural settings, its capacity to utilize a human lung-expressed receptor underscores the importance of monitoring bat-borne viruses with predicted zoonotic potential. Continued surveillance in regions where humans and wildlife interact closely remains essential to detect any future changes in viral behavior.
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