Interferon γ expressed by a recombinant respiratory syncytial virus attenuates virus replication in mice without compromising immunogenicity

Alexander Bukreyev, Stephen S. Whitehead, Natalya Bukreyeva, Brian R. Murphy, Peter L. Collins

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Interferon γ (IFN-γ) has pleiotropic biological effects, including intrinsic antiviral activity as well as stimulation and regulation of immune responses. An infectious recombinant human respiratory syncytial virus (rRSV/mIFN-γ) was constructed that encodes murine (m) IFN-γ as a separate gene inserted into the G-F intergenic region. Cultured cells infected with rRSV/mIFN-γ secreted 22 μg mIFN-γ per 106 cells. The replication of rRSV/mIFN-γ but not that of a control chimeric rRSV containing the chloramphenicol acetyl transferase (CAT) gene as an additional gene, was 63- and 20-fold lower than that of wild-type (wt) RSV in the upper and lower respiratory tract, respectively, of mice. Thus, the attenuation of rRSV/mIFN- γ in vivo could be attributed to the activity of mIFN-γ and not to the presence of the additional gene per se. The mice were completely resistant to subsequent challenge with wt RSV. Despite its growth restriction, infection of mice with rRSV/mIFN-γ induced a level of RSV-specific antibodies that, on day 56, was comparable to or greater than that induced by infection with wt RSV. Mice infected with rRSV/mIFN-γ developed a high level of IFN-γ mRNA and an increased amount of interleukin 12 p40 mRNA in their lungs, whereas other cytokine mRNAs tested were unchanged compared with those induced by wt RSV. Because attenuation of RSV typically is accompanied by a reduction in immunogenicity, expression of IFN-γ by an rRSV represents a method of attenuation in which immunogenicity can be maintained rather than be reduced.

Original languageEnglish (US)
Pages (from-to)2367-2372
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number5
DOIs
StatePublished - Mar 2 1999
Externally publishedYes

Fingerprint

Respiratory Syncytial Viruses
Virus Replication
Interferons
Messenger RNA
Genes
Human respiratory syncytial virus
Intergenic DNA
Chloramphenicol
Interleukin-12
Transferases
Infection
Respiratory System
Antiviral Agents
Cultured Cells
Cytokines
Lung
Antibodies
Growth

Keywords

  • Cytokine
  • Immunization
  • Paramynovirus
  • Vaccine

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Interferon γ expressed by a recombinant respiratory syncytial virus attenuates virus replication in mice without compromising immunogenicity. / Bukreyev, Alexander; Whitehead, Stephen S.; Bukreyeva, Natalya; Murphy, Brian R.; Collins, Peter L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 5, 02.03.1999, p. 2367-2372.

Research output: Contribution to journalArticle

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