Journal article
T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice
Journal of virology, Vol.84(18), pp.9318-9325
09/2010
DOI: 10.1128/JVI.01049-10
PMCID: PMC2937604
PMID: 20610717
Abstract
A dysregulated innate immune response and exuberant cytokine/chemokine expression are believed to be critical factors in the pathogenesis of severe acute respiratory syndrome (SARS), caused by a coronavirus (SARS-CoV). However, we recently showed that inefficient immune activation and a poor virus-specific T cell response underlie severe disease in SARS-CoV-infected mice. Here, we extend these results to show that virus-specific T cells, in the absence of activation of the innate immune response, were sufficient to significantly enhance survival and diminish clinical disease. We demonstrated that T cells are responsible for virus clearance, as intravenous adoptive transfer of SARS-CoV-immune splenocytes or in vitro-generated T cells to SCID or BALB/c mice enhanced survival and reduced virus titers in the lung. Enhancement of the number of virus-specific CD8 T cells by immunization with SARS-CoV peptide-pulsed dendritic cells also resulted in a robust T cell response, earlier virus clearance, and increased survival. These studies are the first to show that T cells play a crucial role in SARS-CoV clearance and that a suboptimal T cell response contributes to the pathological changes observed in SARS. They also provide a new approach to SARS vaccine design.
Details
- Title: Subtitle
- T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice
- Creators
- Jincun Zhao - Department of Microbiology, University of Iowa, 3-712 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242, USAJingxian ZhaoStanley Perlman
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.84(18), pp.9318-9325
- DOI
- 10.1128/JVI.01049-10
- PMID
- 20610717
- PMCID
- PMC2937604
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- United States
- Grant note
- P01 AI060699 / NIAID NIH HHS R56AI079429 / NIAID NIH HHS R21 AI079429 / NIAID NIH HHS
- Language
- English
- Date published
- 09/2010
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777474002771
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