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Adaptive Evolution of MERS-CoV to Species Variation in DPP4.
Cell Rep. 2018 08 14; 24(7):1730-1737.CR

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption. Passaging virus on cells expressing this DPP4 variant led to accumulation of mutations in the viral spike which increased replication. Parallel passages revealed distinct paths of viral adaptation to the same DPP4 variant. Structural analysis and functional assays showed that these mutations enhanced viral entry with suboptimal DPP4 by altering the surface charge of spike. These findings demonstrate that MERS-CoV spike can utilize multiple paths to rapidly adapt to novel species variation in DPP4.

Authors+Show Affiliations

Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. Electronic address: michael.letko@nih.gov.Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA; Department of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, USA.Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA; Department of Microbiology, Immunology, & Pathology, Colorado State University, Fort Collins, CO 80523, USA.Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. Electronic address: vincent.munster@nih.gov.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30110630

Citation

Letko, Michael, et al. "Adaptive Evolution of MERS-CoV to Species Variation in DPP4." Cell Reports, vol. 24, no. 7, 2018, pp. 1730-1737.
Letko M, Miazgowicz K, McMinn R, et al. Adaptive Evolution of MERS-CoV to Species Variation in DPP4. Cell Rep. 2018;24(7):1730-1737.
Letko, M., Miazgowicz, K., McMinn, R., Seifert, S. N., Sola, I., Enjuanes, L., Carmody, A., van Doremalen, N., & Munster, V. (2018). Adaptive Evolution of MERS-CoV to Species Variation in DPP4. Cell Reports, 24(7), 1730-1737. https://doi.org/10.1016/j.celrep.2018.07.045
Letko M, et al. Adaptive Evolution of MERS-CoV to Species Variation in DPP4. Cell Rep. 2018 08 14;24(7):1730-1737. PubMed PMID: 30110630.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adaptive Evolution of MERS-CoV to Species Variation in DPP4. AU - Letko,Michael, AU - Miazgowicz,Kerri, AU - McMinn,Rebekah, AU - Seifert,Stephanie N, AU - Sola,Isabel, AU - Enjuanes,Luis, AU - Carmody,Aaron, AU - van Doremalen,Neeltje, AU - Munster,Vincent, PY - 2018/04/03/received PY - 2018/06/13/revised PY - 2018/07/12/accepted PY - 2018/8/16/entrez PY - 2018/8/16/pubmed PY - 2019/11/26/medline KW - Adaptation KW - Bat KW - Coronavirus KW - DPP4 KW - Desmodus rotundus KW - Dipeptidyl peptidase IV KW - Evolution KW - MERS KW - Species barrier KW - Spike KW - Zoonosis SP - 1730 EP - 1737 JF - Cell reports JO - Cell Rep VL - 24 IS - 7 N2 - Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption. Passaging virus on cells expressing this DPP4 variant led to accumulation of mutations in the viral spike which increased replication. Parallel passages revealed distinct paths of viral adaptation to the same DPP4 variant. Structural analysis and functional assays showed that these mutations enhanced viral entry with suboptimal DPP4 by altering the surface charge of spike. These findings demonstrate that MERS-CoV spike can utilize multiple paths to rapidly adapt to novel species variation in DPP4. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/30110630/Adaptive_Evolution_of_MERS_CoV_to_Species_Variation_in_DPP4_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(18)31148-3 DB - PRIME DP - Unbound Medicine ER -