Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model

Mark J. Cameron, Alyson A. Kelvin, Alberto J. Leon, Cheryl M. Cameron, Longsi Ran, Luoling Xu, Yong Kyu Chu, Ali Danesh, Yuan Fang, Qianjun Li, Austin Anderson, Ronald C. Couch, Stephane G. Paquette, Ndingsa G. Fomukong, Otfried Kistner, Manfred Lauchart, Thomas Rowe, Kevin S. Harrod, Colleen Jonsson, David J. Kelvin

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)3-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.

Original languageEnglish (US)
Article numbere45842
JournalPLoS One
Volume7
Issue number9
DOIs
StatePublished - Sep 24 2012
Externally publishedYes

Fingerprint

Coronavirus Infections
SARS Virus
Ferrets
Coronavirinae
ferrets
interferons
Interferons
Vaccination
Vaccines
vaccination
Viruses
Gene expression
infection
Antiviral Agents
vaccines
Pathology
Genes
immunity
lungs
Immunity

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Cameron, M. J., Kelvin, A. A., Leon, A. J., Cameron, C. M., Ran, L., Xu, L., ... Kelvin, D. J. (2012). Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model. PLoS One, 7(9), [e45842]. https://doi.org/10.1371/journal.pone.0045842

Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model. / Cameron, Mark J.; Kelvin, Alyson A.; Leon, Alberto J.; Cameron, Cheryl M.; Ran, Longsi; Xu, Luoling; Chu, Yong Kyu; Danesh, Ali; Fang, Yuan; Li, Qianjun; Anderson, Austin; Couch, Ronald C.; Paquette, Stephane G.; Fomukong, Ndingsa G.; Kistner, Otfried; Lauchart, Manfred; Rowe, Thomas; Harrod, Kevin S.; Jonsson, Colleen; Kelvin, David J.

In: PLoS One, Vol. 7, No. 9, e45842, 24.09.2012.

Research output: Contribution to journalArticle

Cameron, MJ, Kelvin, AA, Leon, AJ, Cameron, CM, Ran, L, Xu, L, Chu, YK, Danesh, A, Fang, Y, Li, Q, Anderson, A, Couch, RC, Paquette, SG, Fomukong, NG, Kistner, O, Lauchart, M, Rowe, T, Harrod, KS, Jonsson, C & Kelvin, DJ 2012, 'Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model', PLoS One, vol. 7, no. 9, e45842. https://doi.org/10.1371/journal.pone.0045842
Cameron, Mark J. ; Kelvin, Alyson A. ; Leon, Alberto J. ; Cameron, Cheryl M. ; Ran, Longsi ; Xu, Luoling ; Chu, Yong Kyu ; Danesh, Ali ; Fang, Yuan ; Li, Qianjun ; Anderson, Austin ; Couch, Ronald C. ; Paquette, Stephane G. ; Fomukong, Ndingsa G. ; Kistner, Otfried ; Lauchart, Manfred ; Rowe, Thomas ; Harrod, Kevin S. ; Jonsson, Colleen ; Kelvin, David J. / Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model. In: PLoS One. 2012 ; Vol. 7, No. 9.
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