Adaptive Evolution of MERS-CoV to Species Variation in DPP4

Letko, Michael; Miazgowicz, Kerri L.; McMinn, Rebekah J; Seifert, Stephanie N.; Sola, Isabel; Enjuanes, Luis; Carmody, Aaron B.; Doremalen, Neeltje van; Munster, Vincent J.

doi:10.1016/j.celrep.2018.07.045

Cited by 114 publications

(137 citation statements)

References 36 publications

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“…Notably, although P. pipistrellus bCD26 displayed too weak an interaction with MERS-RBD to be detected by FACS, P. pipistrellus bCD26 still supported MERS-CoV entry ( Fig. 3B), consistent with previous results (17,24). Therefore, all bCD26s tested bound to MERS-RBD and mediated MERS-CoV entry, despite their different binding affinities.…”

supporting

confidence: 89%

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Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species

Yuan

Peng

et al. 2020

J Virol

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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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supporting

confidence: 89%

“…Experimentally, bat CD26s (bCD26s) from a diverse range of bat species can mediate the entry of MERS-CoV (17). Cell lines from certain species of bats also support the replication of MERS-CoV (18).…”

mentioning

confidence: 99%

Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species

Yuan

Peng

et al. 2020

J Virol

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“…Previous studies showed that CoVs genomes display a high degree of plasticity in terms of gene content and recombination. Furthermore, the relatively large CoV genome increases the probabilities for adaptive mutations, with it being relative easy for the spike protein to exploit multiple cellular receptors for virus attachment and entry [52,[77][78][79]. These features are likely the cause of this alarming propensity of CoVs for host-species expansion.…”

Section: Discussionmentioning

confidence: 99%

COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives

Sun

Wang

et al. 2020

Trends in Molecular Medicine

580

526

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“…CoV spike pseudotypes were produced as previously described 31 . 293T cells were seeded onto six-well plates pre-coated with poly-l-lysine (Sigma-Aldrich) and transfected the next day with 1,200 ng of empty plasmid and 400 ng of plasmid encoding coronavirus spike or green fluorescent protein (GFP) as a no-spike control.…”

Section: Methodsmentioning

confidence: 99%

“…Unfortunately, a common problem with studies assessing viral entry in cell types from different species is accurately measuring surface protein expression of the receptor through conventional methods such as flow cytometry. We have previously shown that DPP4 from different species crossreacts differently with the same DPP4 antibody, confounding correlations between receptor expression level and entry 31 .…”

Section: Articlesmentioning

confidence: 99%