Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice.

Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice. Research Abstract Details 

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Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice. Abstract Text:

Barry Rockx,Timothy Sheahan,Eric Donaldson,Jack Harkema,Amy Sims,Mark Heise,Raymond Pickles,Mark Cameron,David Kelvin,Ralph Baric,

The severe acute respiratory syndrome (SARS) epidemic was characterized by high mortality rates in the elderly. The molecular mechanisms that govern enhanced susceptibility of elderly populations are not known, and robust animal models are needed that recapitulate the increased pathogenic phenotype noted with increasing age. Using synthetic biology and reverse genetics, we describe the construction of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike glycoproteins that are representative of zoonotic strains found in palm civets and raccoon dogs, as well as isolates spanning the early, middle, and late phases of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell culture and demonstrated variable sensitivities to neutralization with antibodies. The human but not the zoonotic variants replicated efficiently in human airway epithelial cultures, supporting earlier hypotheses that zoonotic isolates are less pathogenic in humans but can evolve into highly pathogenic strains. All viruses replicated efficiently, but none produced clinical disease or death in young animals. In contrast, severe clinical disease, diffuse alveolar damage, hyaline membrane formation, alveolitis, and death were noted in 12-month-old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase GZ02 variants but not with related middle- and late-phase epidemic or raccoon dog strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic spike glycoproteins will provide heterologous challenge models for testing vaccine efficacy against zoonotic reintroductions as well as provide the appropriate model system for elucidating the complex virus-host interactions that contribute to more-severe and fatal SARS-CoV disease and acute respiratory distress in the elderly.

Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice. Publishing Authors By Initials

B Rockx,T Sheahan,E Donaldson,J Harkema,A Sims,M Heise,R Pickles,M Cameron,D Kelvin,R Baric,

For similar bacterial infections and mycoses: zoonoses research abstracts see: bacterial infections and mycoses: zoonoses research

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Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of virology

VOLUME: 81

Page Numbers: 7410-23

Journal Abbreviation: J. Virol.

ISSN: 0022-538X

DAY: 16

MONTH: 05

YEAR: 2007

Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 113724

Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice. Keywords Mesh Terms:

KEYWORDS: Zoonoses

MESH TERMS: genetics

Chemical & Substance for Abstract: Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice. Information

Substance Name: spike glycoprotein, coronavirus

Registry Number: 107476-75-5

Grant and Affiliation Information for Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice.

AFFILIATION: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27699-7435, USA.

Country: United States

AGENCY: United States NIAID

GRANT: P01 AI059443

ACRONYM: AI

MEDLINETA: J Virol

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