The NS2 protein of human respiratory syncytial virus suppresses the cytotoxic T-cell response as a consequence of suppressing the type I interferon response

Alexander Kotelkin, Igor M. Belyakov, Lijuan Yang, Jay A. Berzofsky, Peter L. Collins, Alexander Bukreyev

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The NS1 and NS2 proteins of human respiratory syncytial virus (HRSV) have been shown to antagonize the type I interferon (IFN) response, an effect subject to host range constraints. We have now found that the HRSV NS2 protein strongly controls IFN induction in mouse cells in vitro, validating the use of the mouse model to study the consequences of these gene deletions on host immunity. We evaluated the effects of deleting the NS1 and/or NS2 gene on the induction of HRSV-specific pulmonary cytotoxic T lymphocytes (CTL) in BALB/c and 129S6 mice in response to intranasal infection with HRSV lacking the NS1 and/or NS2 gene and subsequent challenge with wild-type (wt) HRSV. In mice infected with HRSV lacking the NS2 gene (ΔNS2) or lacking the NS2 gene in combination with the NS1 gene (ΔNS1/2 HRSV), the magnitude of the pulmonary CTL response was substantially elevated compared to that of mice infected with wt HRSV or the ΔNS1 mutant, whether measured by binding of CD8+ cells to an HRSV-specific major histocompatibility complex class I tetramer, by measurement of CD8+ cells secreting gamma interferon (IFN-γ) in response to specific in vitro stimulation, or by a standard chromium release cell-killing assay. In contrast, in STAT1 knockout mice, which lack responsiveness to type I IFN, the level of IFN-γ-secreting CD8+ cells was not significantly different for HRSV lacking the NS2 gene, suggesting that the increase in CTL observed in IFN-responsive mice is type I IFN dependent. Thus, the NS2 protein of HRSV suppresses the CTL component of the adaptive immune response, and this appears to be a consequence of its suppression of type I IFN.

Original languageEnglish (US)
Pages (from-to)5958-5967
Number of pages10
JournalJournal of Virology
Volume80
Issue number12
DOIs
StatePublished - Jun 2006
Externally publishedYes

Fingerprint

Human respiratory syncytial virus
Interferon Type I
interferons
T-lymphocytes
T-Lymphocytes
Cytotoxic T-Lymphocytes
cytotoxic T-lymphocytes
proteins
Interferons
Genes
mice
genes
cells
Lung
human respiratory syncytial virus NS2 protein
Host Specificity
Gene Deletion
lungs
Adaptive Immunity
Chromium

ASJC Scopus subject areas

  • Immunology

Cite this

The NS2 protein of human respiratory syncytial virus suppresses the cytotoxic T-cell response as a consequence of suppressing the type I interferon response. / Kotelkin, Alexander; Belyakov, Igor M.; Yang, Lijuan; Berzofsky, Jay A.; Collins, Peter L.; Bukreyev, Alexander.

In: Journal of Virology, Vol. 80, No. 12, 06.2006, p. 5958-5967.

Research output: Contribution to journalArticle

Kotelkin, Alexander ; Belyakov, Igor M. ; Yang, Lijuan ; Berzofsky, Jay A. ; Collins, Peter L. ; Bukreyev, Alexander. / The NS2 protein of human respiratory syncytial virus suppresses the cytotoxic T-cell response as a consequence of suppressing the type I interferon response. In: Journal of Virology. 2006 ; Vol. 80, No. 12. pp. 5958-5967.
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