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A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry
Jing Chen1, Xinglou Yang1, Haorui Si2
1CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Abstract:
It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.
Insights
Pangolins harbor a novel MERS-like coronavirus (MjHKU4r-CoV) capable of infecting humans. This virus, infectious in human cells and mice, highlights pangolins as potential reservoirs for emerging coronaviruses.
Area of Science:
- Virology
- Zoonotic Diseases
- Mammalian Reservoir Hosts
Background:
- Pangolins are the most trafficked mammals globally.
- The role of pangolins in the zoonotic transmission of bat coronaviruses remains unclear.
Purpose of the Study:
- To investigate the presence and characteristics of coronaviruses in pangolins.
- To assess the potential of pangolin-associated coronaviruses to infect humans.
Main Methods:
- Pan-coronavirus PCR and serological testing on pangolin samples.
- Genome sequencing and virus isolation.
- In vitro studies using human cell lines and hDPP4-transgenic mice.
Main Results:
- A novel MERS-like coronavirus (MjHKU4r-CoV) was detected in Malayan pangolins.
- MjHKU4r-CoV utilizes human DPP4 as a receptor and possesses enhanced cell entry mechanisms.
- The isolated virus (MjHKU4r-CoV-1) demonstrated infectivity and pathogenicity in human airway and intestinal models, including hDPP4-transgenic mice.
Conclusions:
- Pangolins can act as reservoir hosts for coronaviruses with pandemic potential.
- MjHKU4r-CoV represents a significant zoonotic threat due to its ability to infect human cells and organs.
- The findings underscore the importance of monitoring wildlife, particularly trafficked species like pangolins, for novel viruses.
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