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.

Interferon induction by viruses. VI. Reovirus: virion genome dsRNA as the interferon inducer in aged chick embryo cells.

The interferon-inducing particle (IFP) activity of avian and human reoviruses in aged chick embryo cells was determined by analyzing dose (multiplicity)-response (interferon yield) curves. These curves fit best a model in which each cell infected with greater than or equal to 1 IFP produces a quantum yield of interferon. Avian reovirus stocks contained as many as 60 times more IFP than plaque-forming particles (PFP). Upon UV-irradiation the ratio of IFP:PFP became 197, suggesting that virtually every physical particle of avian reovirus could function as an interferon-inducing particle. Thus, about one-third of the non-infectious particles were intrinsically IFP and the other two-thirds could be converted to IFP status at an optimal dose of UV radiation, the equivalent of 9.4 lethal hits, i.e., 8000 ergs/mm2. UV-irradiated avian reovirus induced about twice the usual yield of interferon on a per cell basis. Wildtype human reovirus (type 3) and mutants ts201(A,RNA+) and ts447(C,RNA-) were excellent inducers of interferon, but only about 1 in 3 infectious particles functioned as an interferon-inducing particle, meaning that virtually all physical particles failed to function as IFP, UV-irradiation of human reoviruses resulted in a slight loss of IFP activity. Our data support the hypothesis that virion genome dsRNA constitutes the interferon inducer moiety of avian reoviruses and that in its permissive host cell the processing of genome dsRNA from most particles to a putative recognition site in the cytoplasm occurs naturally with a high probability. For human reovirus this is a much rarer event which may be intrinsic only to infectious virus, and may require limited transcription for expression. The sensitivity of the avian reovirus-aged chick embryo cell system recommends it for further study on the mechanism of interferon induction by virions containing pre-existing dsRNA.

[Interferon-producing activity of bone marrow cells treated with mRNA for interferon when transplanted to irradiated mice]. / Interferonprodutsiruiushchaia aktivnost' kletok kostnogo mozga, obrabotannykh iRNK dlia interferona, pri transplantatsii ikh obluchennym mysham.

Inoculation into irradiated (800--850 r) mice of syngeneic bone marrow cells treated with mRNA for interferon (mRNA-If) obtained from chick cells induced with UV-irradiated Newcastle disease virus was accompanied by the appearance in the blood of the animals of a substance with the properties of interferon, inhibiting the cytopathic effect of vesicular stomatitis virus in chick embryo cells but not in mouse L cells. Chicken interferon was detected in the blood of the experimental animals for 7--10 days after transplantation of mRNA-If-treated cells.

[Influence of whole-body irradiation with 60Co on poly I:C induced interferon in mice (author's transl)]. / Einfluss von Ganzköperbestrahlung mit 60Co auf die interferoninduktion durch Poly I:C bei Mäusen

After whole-body irradiation with 200, 900 und 1500 R on mice Poly I:C induced serum interferon was decreased. 24 and 48 hours p.r. the interferon-synthesis in the three irradiated groups was considerably reduced. Increasing interferon-titer-yet lower than those of not irradiated controls - were found after Poly I:C application 3, 4 and 5 days p.r. in the groups irradiated with 200 and 900 R. In these two groups a relationship between irradiation-dose and interferon-synthesis was recognized.