Sendai virus and simian virus 5 block activation of interferon-responsive genes: Importance for virus pathogenesis

Sendai virus (SeV) is highly pathogenic for mice. In contrast, mice (includ ing SCID mice) infected with simian virus 5 (SV5) showed no overt signs of disease. Evidence is presented that a major factor which prevented SV5 from productively infecting mice was its inability to circumvent the interferon (IFN) response in mice. Thus, in murine cells that produce and respond to IFN, SV5 protein synthesis was rapidly switched off. In marked contrast, on ce SeV protein synthesis began, it continued, even if the culture medium wa s supplemented with alpha/beta IFN (IFN-alpha/beta). However, in human cell s, IFN-alpha/beta did not inhibit the replication of either SV5 or SeV once virus protein synthesis was established. To begin to address the molecular basis for these observations, the effects of SeV and SV5 infections on the activation of an IFN-alpha/beta-responsive promoter and on that of the IFN -beta promoter were examined in transient transfection experiments. The res ults demonstrated that (i) SeV, but not SV5, inhibited an IFN-alpha/beta-re sponsive promoter in murine cells; (ii) both SV5 and SeV inhibited the acti vation of an IFN-alpha/beta-responsive promoter in human cells; and (iii) i n both human and murine cells, SeV was a strong inducer of the IFN-beta pro moter, whereas SV5 was a poor inducer. The ability of SeV and SV5 to inhibi t the activation of IFN-responsive genes in human cells was confirmed by RN ase protection experiments. The importance of these results in terms of par amyxovirus pathogenesis is discussed.