Effect of coexpression of interleukin-2 by recombinant respiratory syncytial virus on virus replication, immunogenicity, and production of other cytokines

Alexander Bukreyev, Stephen S. Whitehead, Calman Prussin, Brian R. Murphy, Peter L. Collins

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

We constructed rRSV/mIL-2, a recombinant respiratory syncytial virus (rRSV) containing the coding sequence of murine interleukin-2 (mIL-2) in a transcription cassette inserted into the G-F intergenic region. The recovered virus (rRSV/mIL-2) expressed high levels (up to 2.8 ug/ml) of mIL-2 in cell culture. Replication of rRSV/mIL-2 in vitro was reduced up to 13.6-fold from that of wild-type (wt) rRSV, an effect that was due to the presence of the foreign insert but was not specific to mIL-2. Replication of the rRSV/mIL-2 virus in the upper and lower respiratory tracts of BALB/c mice was reduced up to 6.3-fold, an effect that was specific to mIL-2. The antibody response, including the levels of RSV-specific serum immunoglobulin G1 (IgG1), IgG2a, IgA, and total IgG, and the level of protective efficacy against wt RSV challenge were not significantly different from those of wt rRSV. Analysis of total pulmonary cytokine mRNA isolated 1 and 4 days following infection with rRSV/mIL-2 revealed elevated levels of mRNA for IL-2, gamma interferon (IFN- γ), IL-4, IL-5, IL-6, IL-10, IL-13, and IL-12 p40 compared to those for wt rRSV. Flow cytometry of total pulmonary mononuclear cells isolated 10 days following infection with rRSV/mIL-2 revealed increased levels of CD4+ T lymphocytes expressing either IFN-γ or IL-4 compared to those of wt rRSV. These elevations in cytokine mRNA or cytokine-expressing CD4+ cells relative to those of wt rRSV-primed animals were not observed following challenge with wt RSV on day 28. Thus, the expression of mIL-2 by rRSV was associated with a modest attenuation of virus growth in vivo, induction of serum antibodies at levels comparable to that of wt rRSV, and transient increases in both the Th1 and Th2 CD4+ lymphocytes and cytokine mRNAs compared to those of wt rRSV.

Original languageEnglish (US)
Pages (from-to)7151-7157
Number of pages7
JournalJournal of Virology
Volume74
Issue number15
DOIs
StatePublished - Aug 2000
Externally publishedYes

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Respiratory Syncytial Viruses
Virus Replication
virus replication
interleukin-2
Interleukin-2
cytokines
immune response
Cytokines
viruses
mice
Messenger RNA
Viruses
Interleukin-4
interleukin-4
lungs
Lung
Intergenic DNA
Interleukin-13
Interleukin-5
interleukin-5

ASJC Scopus subject areas

  • Immunology

Cite this

Effect of coexpression of interleukin-2 by recombinant respiratory syncytial virus on virus replication, immunogenicity, and production of other cytokines. / Bukreyev, Alexander; Whitehead, Stephen S.; Prussin, Calman; Murphy, Brian R.; Collins, Peter L.

In: Journal of Virology, Vol. 74, No. 15, 08.2000, p. 7151-7157.

Research output: Contribution to journalArticle

Bukreyev, Alexander ; Whitehead, Stephen S. ; Prussin, Calman ; Murphy, Brian R. ; Collins, Peter L. / Effect of coexpression of interleukin-2 by recombinant respiratory syncytial virus on virus replication, immunogenicity, and production of other cytokines. In: Journal of Virology. 2000 ; Vol. 74, No. 15. pp. 7151-7157.
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AU - Whitehead, Stephen S.

AU - Prussin, Calman

AU - Murphy, Brian R.

AU - Collins, Peter L.

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N2 - We constructed rRSV/mIL-2, a recombinant respiratory syncytial virus (rRSV) containing the coding sequence of murine interleukin-2 (mIL-2) in a transcription cassette inserted into the G-F intergenic region. The recovered virus (rRSV/mIL-2) expressed high levels (up to 2.8 ug/ml) of mIL-2 in cell culture. Replication of rRSV/mIL-2 in vitro was reduced up to 13.6-fold from that of wild-type (wt) rRSV, an effect that was due to the presence of the foreign insert but was not specific to mIL-2. Replication of the rRSV/mIL-2 virus in the upper and lower respiratory tracts of BALB/c mice was reduced up to 6.3-fold, an effect that was specific to mIL-2. The antibody response, including the levels of RSV-specific serum immunoglobulin G1 (IgG1), IgG2a, IgA, and total IgG, and the level of protective efficacy against wt RSV challenge were not significantly different from those of wt rRSV. Analysis of total pulmonary cytokine mRNA isolated 1 and 4 days following infection with rRSV/mIL-2 revealed elevated levels of mRNA for IL-2, gamma interferon (IFN- γ), IL-4, IL-5, IL-6, IL-10, IL-13, and IL-12 p40 compared to those for wt rRSV. Flow cytometry of total pulmonary mononuclear cells isolated 10 days following infection with rRSV/mIL-2 revealed increased levels of CD4+ T lymphocytes expressing either IFN-γ or IL-4 compared to those of wt rRSV. These elevations in cytokine mRNA or cytokine-expressing CD4+ cells relative to those of wt rRSV-primed animals were not observed following challenge with wt RSV on day 28. Thus, the expression of mIL-2 by rRSV was associated with a modest attenuation of virus growth in vivo, induction of serum antibodies at levels comparable to that of wt rRSV, and transient increases in both the Th1 and Th2 CD4+ lymphocytes and cytokine mRNAs compared to those of wt rRSV.

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