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

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

DOI: 10.1128/JVI.74.15.7151-7157.2000

关键词:

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

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