Coronavirus antibodies in African bat species.
Ontology highlight
ABSTRACT:
SUBMITTER: Muller MA
PROVIDER: S-EPMC2857293 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Continued reports of Middle East respiratory syndrome coronavirus (MERS-CoV) infecting humans have occurred since the identification of this virus in 2012. MERS-CoV is prone to cause endemic disease in the Middle East, with several dozen spillover infections to other continents. It is hypothesized that MERS-CoV originated from bat coronaviruses and that dromedary camels are its natural reservoir. Although gene segments identical to MERS-CoV were sequenced from certain species of bats and one species experimentally shed the virus, it is still unknown whether other bats can transmit the virus. Here, at the molecular level, we found that all purified bat CD26s (bCD26s) from a diverse range of species interact with the receptor binding domain (RBD) of MERS-CoV, with equilibrium dissociation constant values ranging from several to hundreds at the micromolar level. Moreover, all bCD26s expressed in this study mediated the entry of pseudotyped MERS-CoV to receptor-expressing cells, indicating the broad potential engagement of bCD26s as MERS-CoV receptors. Further structural analysis indicated that in the bat receptor, compared to the human receptor, substitutions of key residues and their adjacent amino acids leads to decreased binding affinity to the MERS-RBD. These results add more evidence to the existing belief that bats are the original source of MERS-CoV and suggest that bCD26s in many species can mediate the entry of the virus, which has significant implications for the surveillance and control of MERS-CoV infection.IMPORTANCE In this study, we found that bat CD26s (bCD26s) from different species exhibit large diversities, especially in the region responsible for binding to the receptor binding domain (RBD) of Middle East respiratory syndrome coronavirus (MERS-CoV). However, they maintain the interaction with MERS-RBD at varied affinities and support the entry of pseudotyped MERS-CoV. These bat receptors polymorphisms seem to confer evolutionary pressure for the adaptation of CD26-binding virus, such as the ancestor of MERS-CoV, and led to the generation of diversified CD26-engaging CoV strains. Thus, our data add more evidence to support that bats are the reservoir of MERS-CoV and similar viruses, as well as further emphasize the necessity to survey MERS-CoV and other CoVs among bats.
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Project description:Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes ? 36% fatality in infected patients. Believed to have originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4 and HKU5. To understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of HKU4 and HKU5. We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS-CoV, is also the receptor for HKU4, but not HKU5. Despite sharing a common receptor, MERS-CoV and HKU4 spikes demonstrated functional differences. First, whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV spike, but not HKU4 spike, mediates pseudovirus entry into human cells. Thus, MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular proteases for efficient human cell entry, contributing to the enhanced pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional receptor for HKU4 and host cellular proteases as a host range determinant for HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human health because of their spikes' capability to adapt to human cells for cross-species transmissions.
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Project description:The recent outbreak of severe respiratory infections associated with a novel group C betacoronavirus (HCoV-EMC) from Saudi Arabia has drawn global attention to another highly probable "SARS-like" animal-to-human interspecies jumping event in coronavirus (CoV). The genome of HCoV-EMC is most closely related to Tylonycteris bat coronavirus HKU4 (Ty-BatCoV HKU4) and Pipistrellus bat coronavirus HKU5 (Pi-BatCoV HKU5) we discovered in 2006. Phylogenetically, HCoV-EMC is clustered with Ty-BatCoV HKU4/Pi-BatCoV HKU5 with high bootstrap supports, indicating that HCoV-EMC is a group C betaCoV. The major difference between HCoV-EMC and Ty-BatCoV HKU4/Pi-BatCoV HKU5 is in the region between S and E, where HCoV-EMC possesses five ORFs (NS3a-NS3e) instead of four, with low (31%-62%) amino acid identities to Ty-BatCoV HKU4/Pi-BatCoV HKU5. Comparison of the seven conserved replicase domains for species demarcation shows that HCoV-EMC is a novel CoV species. More intensive surveillance studies in bats and other animals may reveal the natural host of HCoV-EMC.
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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.
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Project description:UnlabelledThe emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes lethal respiratory infections mainly on the Arabian Peninsula. The evolutionary origins of MERS-CoV are unknown. We determined the full genome sequence of a CoV directly from fecal material obtained from a South African Neoromicia capensis bat (NeoCoV). NeoCoV shared essential details of genome architecture with MERS-CoV. Eighty-five percent of the NeoCoV genome was identical to MERS-CoV at the nucleotide level. Based on taxonomic criteria, NeoCoV and MERS-CoV belonged to one viral species. The presence of a genetically divergent S1 subunit within the NeoCoV spike gene indicated that intraspike recombination events may have been involved in the emergence of MERS-CoV. NeoCoV constitutes a sister taxon of MERS-CoV, placing the MERS-CoV root between a recently described virus from African camels and all other viruses. This suggests a higher level of viral diversity in camels than in humans. Together with serologic evidence for widespread MERS-CoV infection in camelids sampled up to 20 years ago in Africa and the Arabian Peninsula, the genetic data indicate that camels act as sources of virus for humans rather than vice versa. The majority of camels on the Arabian Peninsula is imported from the Greater Horn of Africa, where several Neoromicia species occur. The acquisition of MERS-CoV by camels from bats might have taken place in sub-Saharan Africa. Camelids may represent mixing vessels for MERS-CoV and other mammalian CoVs.ImportanceIt is unclear how, when, and where the highly pathogenic MERS-CoV emerged. We characterized the full genome of an African bat virus closely related to MERS-CoV and show that human, camel, and bat viruses belong to the same viral species. The bat virus roots the phylogenetic tree of MERS-CoV, providing evidence for an evolution of MERS-CoV in camels that preceded that in humans. The revised tree suggests that humans are infected by camels rather than vice versa. Although MERS-CoV cases occur mainly on the Arabian Peninsula, the data from this study together with serologic and molecular investigations of African camels indicate that the initial host switch from bats may have taken place in Africa. The emergence of MERS-CoV likely involved exchanges of genetic elements between different viral ancestors. These exchanges may have taken place either in bat ancestors or in camels acting as mixing vessels for viruses from different hosts.
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