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10.1080/22221751.2020.1713705

http://scihub22266oqcxt.onion/10.1080/22221751.2020.1713705
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31964246!7006675!31964246
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suck abstract from ncbi


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pmid31964246      Emerg+Microbes+Infect 2020 ; 9 (1): 155-168
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  • Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus #MMPMID31964246
  • Kleine-Weber H; Schroeder S; Kruger N; Prokscha A; Naim HY; Muller MA; Drosten C; Pohlmann S; Hoffmann M
  • Emerg Microbes Infect 2020[]; 9 (1): 155-168 PMID31964246show ga
  • Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Delta346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Delta346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients.
  • |*Virus Internalization[MESH]
  • |Coronavirus Infections/*genetics/immunology/virology[MESH]
  • |Dipeptidyl Peptidase 4/*genetics/immunology[MESH]
  • |Host-Pathogen Interactions[MESH]
  • |Humans[MESH]
  • |Middle East Respiratory Syndrome Coronavirus/genetics/*physiology[MESH]


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