Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection

Rudragouda Channappanavar, Craig Fett, Jincun Zhao, David K. Meyerholz, Stanley Perlman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human respiratory illness with high morbidity and mortality in 2002-2003. Several studies have demonstrated the role of neutralizing antibodies induced by the spike (S) glycoprotein in protecting susceptible hosts from lethal infection. However, the anti-SARS-CoV antibody response is short-lived in patients who have recovered from SARS, making it critical to develop additional vaccine strategies. SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV infection, a time at which memory B cells and antivirus antibodies were undetectable in individuals who had recovered from SARS. In this study, we assessed the ability of virus-specific memory CD8 T cells to mediate protection against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We demonstrate that memory CD8 T cells specific for a single immunodominant epitope (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS-CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs) followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced multiple effector cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B) and reduced lung viral loads. Overall, our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection.

Original languageEnglish (US)
Pages (from-to)11034-11044
Number of pages11
JournalJournal of Virology
Volume88
Issue number19
DOIs
StatePublished - Jan 1 2014

Fingerprint

Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronavirus
T-lymphocytes
Viruses
T-Lymphocytes
viruses
infection
Antibody Formation
antibodies
B-lymphocytes
B-Lymphocytes
SARS Virus
lungs
Severe acute respiratory syndrome coronavirus
Granzymes
Immunodominant Epitopes
Lung
Vaccinia virus
Bronchoalveolar Lavage Fluid

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. / Channappanavar, Rudragouda; Fett, Craig; Zhao, Jincun; Meyerholz, David K.; Perlman, Stanley.

In: Journal of Virology, Vol. 88, No. 19, 01.01.2014, p. 11034-11044.

Research output: Contribution to journalArticle

Channappanavar, Rudragouda ; Fett, Craig ; Zhao, Jincun ; Meyerholz, David K. ; Perlman, Stanley. / Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. In: Journal of Virology. 2014 ; Vol. 88, No. 19. pp. 11034-11044.
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