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Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice.
Proc Natl Acad Sci U S A. 2008 Dec 16; 105(50):19944-9.PN

Abstract

Defining prospective pathways by which zoonoses evolve and emerge as human pathogens is critical for anticipating and controlling both natural and deliberate pandemics. However, predicting tenable pathways of animal-to-human movement has been hindered by challenges in identifying reservoir species, cultivating zoonotic organisms in culture, and isolating full-length genomes for cloning and genetic studies. The ability to design and recover pathogens reconstituted from synthesized cDNAs has the potential to overcome these obstacles by allowing studies of replication and pathogenesis without identification of reservoir species or cultivation of primary isolates. Here, we report the design, synthesis, and recovery of the largest synthetic replicating life form, a 29.7-kb bat severe acute respiratory syndrome (SARS)-like coronavirus (Bat-SCoV), a likely progenitor to the SARS-CoV epidemic. To test a possible route of emergence from the noncultivable Bat-SCoV to human SARS-CoV, we designed a consensus Bat-SCoV genome and replaced the Bat-SCoV Spike receptor-binding domain (RBD) with the SARS-CoV RBD (Bat-SRBD). Bat-SRBD was infectious in cell culture and in mice and was efficiently neutralized by antibodies specific for both bat and human CoV Spike proteins. Rational design, synthesis, and recovery of hypothetical recombinant viruses can be used to investigate mechanisms of transspecies movement of zoonoses and has great potential to aid in rapid public health responses to known or predicted emerging microbial threats.

Authors+Show Affiliations

Departments of Pediatrics and Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19036930

Citation

Becker, Michelle M., et al. "Synthetic Recombinant Bat SARS-like Coronavirus Is Infectious in Cultured Cells and in Mice." Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 50, 2008, pp. 19944-9.
Becker MM, Graham RL, Donaldson EF, et al. Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice. Proc Natl Acad Sci U S A. 2008;105(50):19944-9.
Becker, M. M., Graham, R. L., Donaldson, E. F., Rockx, B., Sims, A. C., Sheahan, T., Pickles, R. J., Corti, D., Johnston, R. E., Baric, R. S., & Denison, M. R. (2008). Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice. Proceedings of the National Academy of Sciences of the United States of America, 105(50), 19944-9. https://doi.org/10.1073/pnas.0808116105
Becker MM, et al. Synthetic Recombinant Bat SARS-like Coronavirus Is Infectious in Cultured Cells and in Mice. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19944-9. PubMed PMID: 19036930.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice. AU - Becker,Michelle M, AU - Graham,Rachel L, AU - Donaldson,Eric F, AU - Rockx,Barry, AU - Sims,Amy C, AU - Sheahan,Timothy, AU - Pickles,Raymond J, AU - Corti,Davide, AU - Johnston,Robert E, AU - Baric,Ralph S, AU - Denison,Mark R, Y1 - 2008/11/26/ PY - 2008/11/28/entrez PY - 2008/11/28/pubmed PY - 2009/1/13/medline SP - 19944 EP - 9 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 105 IS - 50 N2 - Defining prospective pathways by which zoonoses evolve and emerge as human pathogens is critical for anticipating and controlling both natural and deliberate pandemics. However, predicting tenable pathways of animal-to-human movement has been hindered by challenges in identifying reservoir species, cultivating zoonotic organisms in culture, and isolating full-length genomes for cloning and genetic studies. The ability to design and recover pathogens reconstituted from synthesized cDNAs has the potential to overcome these obstacles by allowing studies of replication and pathogenesis without identification of reservoir species or cultivation of primary isolates. Here, we report the design, synthesis, and recovery of the largest synthetic replicating life form, a 29.7-kb bat severe acute respiratory syndrome (SARS)-like coronavirus (Bat-SCoV), a likely progenitor to the SARS-CoV epidemic. To test a possible route of emergence from the noncultivable Bat-SCoV to human SARS-CoV, we designed a consensus Bat-SCoV genome and replaced the Bat-SCoV Spike receptor-binding domain (RBD) with the SARS-CoV RBD (Bat-SRBD). Bat-SRBD was infectious in cell culture and in mice and was efficiently neutralized by antibodies specific for both bat and human CoV Spike proteins. Rational design, synthesis, and recovery of hypothetical recombinant viruses can be used to investigate mechanisms of transspecies movement of zoonoses and has great potential to aid in rapid public health responses to known or predicted emerging microbial threats. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/19036930/Synthetic_recombinant_bat_SARS_like_coronavirus_is_infectious_in_cultured_cells_and_in_mice_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=19036930 DB - PRIME DP - Unbound Medicine ER -