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Pathways of cross-species transmission of synthetically reconstructed zoonotic severe acute respiratory syndrome coronavirus.
J Virol. 2008 Sep; 82(17):8721-32.JV

Abstract

Zoonotic severe acute respiratory syndrome coronavirus (SARS-CoV) likely evolved to infect humans by a series of transmission events between humans and animals in markets in China. Virus sequence data suggest that the palm civet served as an amplification host in which civet and human interaction fostered the evolution of the epidemic SARS Urbani strain. The prototypic civet strain of SARS-CoV, SZ16, was isolated from a palm civet but has not been successfully cultured in vitro. To propagate a chimeric recombinant SARS-CoV bearing an SZ16 spike (S) glycoprotein (icSZ16-S), we constructed cell lines expressing the civet ortholog (DBT-cACE2) of the SARS-CoV receptor (hACE2). Zoonotic SARS-CoV was completely dependent on ACE2 for entry. Urbani grew with similar kinetics in both the DBT-cACE2 and the DBT-hACE2 cells, while icSZ16-S only grew in DBT-cACE2 cells. The SZ16-S mutant viruses adapted to human airway epithelial cells and displayed enhanced affinity for hACE2 but exhibited severe growth defects in the DBT-cACE2 cells, suggesting that the evolutionary pathway that promoted efficient hACE2 interactions simultaneously abolished efficient cACE2 interactions. Structural modeling predicted two distinct biochemical interaction networks by which zoonotic receptor binding domain architecture can productively engage hACE2, but only the Urbani mutational repertoire promoted efficient usage of both hACE2 and cACE2 binding interfaces. Since dual species tropism was preserved in Urbani, it is likely that the virus evolved a high affinity for cACE2/hACE2 receptors through adaptation via repeated passages between human and civet hosts. Furthermore, zoonotic SARS-CoV was variably neutralized by antibodies that were effective against the epidemic strain, highlighting their utility for evaluating passive immunization efficacy.

Authors+Show Affiliations

Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27699-7435, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18579604

Citation

Sheahan, Timothy, et al. "Pathways of Cross-species Transmission of Synthetically Reconstructed Zoonotic Severe Acute Respiratory Syndrome Coronavirus." Journal of Virology, vol. 82, no. 17, 2008, pp. 8721-32.
Sheahan T, Rockx B, Donaldson E, et al. Pathways of cross-species transmission of synthetically reconstructed zoonotic severe acute respiratory syndrome coronavirus. J Virol. 2008;82(17):8721-32.
Sheahan, T., Rockx, B., Donaldson, E., Corti, D., & Baric, R. (2008). Pathways of cross-species transmission of synthetically reconstructed zoonotic severe acute respiratory syndrome coronavirus. Journal of Virology, 82(17), 8721-32. https://doi.org/10.1128/JVI.00818-08
Sheahan T, et al. Pathways of Cross-species Transmission of Synthetically Reconstructed Zoonotic Severe Acute Respiratory Syndrome Coronavirus. J Virol. 2008;82(17):8721-32. PubMed PMID: 18579604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathways of cross-species transmission of synthetically reconstructed zoonotic severe acute respiratory syndrome coronavirus. AU - Sheahan,Timothy, AU - Rockx,Barry, AU - Donaldson,Eric, AU - Corti,Davide, AU - Baric,Ralph, Y1 - 2008/06/25/ PY - 2008/6/27/pubmed PY - 2008/9/30/medline PY - 2008/6/27/entrez SP - 8721 EP - 32 JF - Journal of virology JO - J Virol VL - 82 IS - 17 N2 - Zoonotic severe acute respiratory syndrome coronavirus (SARS-CoV) likely evolved to infect humans by a series of transmission events between humans and animals in markets in China. Virus sequence data suggest that the palm civet served as an amplification host in which civet and human interaction fostered the evolution of the epidemic SARS Urbani strain. The prototypic civet strain of SARS-CoV, SZ16, was isolated from a palm civet but has not been successfully cultured in vitro. To propagate a chimeric recombinant SARS-CoV bearing an SZ16 spike (S) glycoprotein (icSZ16-S), we constructed cell lines expressing the civet ortholog (DBT-cACE2) of the SARS-CoV receptor (hACE2). Zoonotic SARS-CoV was completely dependent on ACE2 for entry. Urbani grew with similar kinetics in both the DBT-cACE2 and the DBT-hACE2 cells, while icSZ16-S only grew in DBT-cACE2 cells. The SZ16-S mutant viruses adapted to human airway epithelial cells and displayed enhanced affinity for hACE2 but exhibited severe growth defects in the DBT-cACE2 cells, suggesting that the evolutionary pathway that promoted efficient hACE2 interactions simultaneously abolished efficient cACE2 interactions. Structural modeling predicted two distinct biochemical interaction networks by which zoonotic receptor binding domain architecture can productively engage hACE2, but only the Urbani mutational repertoire promoted efficient usage of both hACE2 and cACE2 binding interfaces. Since dual species tropism was preserved in Urbani, it is likely that the virus evolved a high affinity for cACE2/hACE2 receptors through adaptation via repeated passages between human and civet hosts. Furthermore, zoonotic SARS-CoV was variably neutralized by antibodies that were effective against the epidemic strain, highlighting their utility for evaluating passive immunization efficacy. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/18579604/Pathways_of_cross_species_transmission_of_synthetically_reconstructed_zoonotic_severe_acute_respiratory_syndrome_coronavirus_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=18579604 DB - PRIME DP - Unbound Medicine ER -