Interferon induction by viruses. XXV. Adenoviruses as inducers of interferon in developmentally aged primary chicken embryo cells.
Chicken embryonic cells (CEC) are nonpermissive hosts for the replication of human adenoviruses, yet they respond to infection by producing interferon (IFN). The nature of the IFN inducer moiety in these viruses has been elusive since its initial study by Ilona Béládi and colleagues some 40 years ago. We tested the hypothesis that viral dsRNA was the IFN inducer molecule--for two reasons: (i) dsRNA has been identified as a potent inducer of IFN, and (ii) developmentally mature CEC cells as cultured in vitro can develop a hyper-responsive state to dsRNA such that a single molecule of dsRNA per cell constitutes the threshold of detection. Furthermore, the number of particles in a virus population capable of inducing-IFN, irrespective of their replication capacity, can be quantified through the analysis of dose (multiplicity)-response (IFN yield) curves, thus allowing a determination of the number particles in virus populations that possess the capacity to induce IFN. This study demonstrates that type 5 wild type adenovirus (Ad5) and mutants dl312, dl334, and ts19 induce from 8,000 to 80,000 IFN U per 10(7) CEC. UV irradiation showed that transcription of about 20-50% of the Ad5 genome was required to produce the IFN inducer moiety. The ratio of IFN-inducing particles to plaque-forming particles (IFP : PFP) was as low as 1:6, indicating that only a small fraction of the total particles in a virus population ever function as IFP. We conclude that adenovirus dsRNA produced during symmetric transcription of some regions of the viral genome, coupled with fine-tuning of the IFN-induction pathway, account for the IFN-inducing capacity of adenoviruses in the non-permissive chicken cell.
Marcus
Ph I
PI
Department of Molecular and Cell Biology, University of Connecticut, Storrs 06269, USA. philip.marcus@uconn.edu
Sekellick
Margaret J
MJ
D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology* / Q000528:radiation effects; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007369:Interferon Inducers / Q000276:immunology* / Q000528:radiation effects; D007372:Interferons / Q000096:biosynthesis*; D014466:Ultraviolet Rays; D014771:Virion / Q000276:immunology / Q000528:radiation effects
D007369:Interferon Inducers; D007372:Interferons