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Structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections.
J Virol. 2008 Jul; 82(14):6984-91.JV

Abstract

It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses.

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Authors+Show Affiliations

Li F
Department of Pharmacology, University of Minnesota Medical School, 6-121 Jackson Hall, 321 Church St. S.E., Minneapolis, MN 55455, USA. lifang@umn.edu

MeSH

Angiotensin-Converting Enzyme 2AnimalsCrystallography, X-RayHumansMembrane GlycoproteinsModels, MolecularPeptidyl-Dipeptidase AProtein Structure, QuaternaryReceptors, VirusRecombination, GeneticSevere acute respiratory syndrome-related coronavirusSevere Acute Respiratory SyndromeSpecies SpecificitySpike Glycoprotein, CoronavirusViral Envelope ProteinsVirus AttachmentViverridae

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18448527

Citation

Li, Fang. "Structural Analysis of Major Species Barriers Between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections." Journal of Virology, vol. 82, no. 14, 2008, pp. 6984-91.
Li F. Structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections. J Virol. 2008;82(14):6984-91.
Li, F. (2008). Structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections. Journal of Virology, 82(14), 6984-91. https://doi.org/10.1128/JVI.00442-08
Li F. Structural Analysis of Major Species Barriers Between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections. J Virol. 2008;82(14):6984-91. PubMed PMID: 18448527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections. A1 - Li,Fang, Y1 - 2008/04/30/ PY - 2008/5/2/pubmed PY - 2008/7/17/medline PY - 2008/5/2/entrez SP - 6984 EP - 91 JF - Journal of virology JO - J Virol VL - 82 IS - 14 N2 - It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/18448527/Structural_analysis_of_major_species_barriers_between_humans_and_palm_civets_for_severe_acute_respiratory_syndrome_coronavirus_infections_ DB - PRIME DP - Unbound Medicine ER -