Cited by 342SARS-CoV-2 and COVID-19 ResearchImmune responses and vaccinationsViral Infections and Outbreaks Research

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T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice

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Zhao, Jincun, Zhao, Jingxian, Perlman, Stanley·2010·Journal of Virology

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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.

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Authors: Zhao, J., Zhao, J., & Perlman, S.
Affiliations: University of Iowa (US)
Corresponding author: Perlman, Stanley
ORCID: Zhao, Jincun
Zhao, Jingxian
Perlman, Stanley
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 2010-09-15
Volume: 84
Issue: 18
Pages: 9318-9325
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.01049-10
PMC: PMC2937604
OpenAlex: W1999546368
Cited by: 340
References: 36
Citations by year: 2026: 2 · 2025: 7 · 2024: 10 · 2023: 28 · 2022: 52 · 2021: 76 · 2020: 122 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 11 · 2015: 4 · 2014: 9 · 2013: 2 · 2012: 4
FWCI: 1.86
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (PO1AI060699, AI060699)
National Institute of Allergy and Infectious Diseases (R21AI079429, R56AI079429, P01AI060699)
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
Keywords: SARS, SARS-CoV, T cell response, CD8+ T cells, viral clearance, adoptive T cell therapy, dendritic cell immunization, innate immune response, lung viral titers, SARS pathogenesis
MeSH terms: Animals, Lung, Mice, Inbred BALB C, Spleen, T-Lymphocytes, Viral Vaccines, Survival Analysis, Mice, SCID, Adoptive Transfer, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Mice

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T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice

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