Characterization of genetically engineered mengoviruses in mice

We have shown that genetically engineered mengoviruses containing artificia lly shortened 5' noncoding poly(C) tracts (e.g., C-0 or C13UC10) are dramat ically attenuated in adult Swiss/ICR mice when compared to wild-type virus or to a genetically engineered virus containing a wild-type length poly(C) tract (C44UC10). To explore further the relationship between poly(C) tracts and virulence, we have conducted more extensive characterizations of sever al engineered viruses in the murine model. Both short and long poly(C) trac t viruses were highly virulent in newborn mice, underscoring the importance of age in poly(C)mediated attenuation. Virus vMC(24), With a tract sequenc e of C13UC10, was as attenuated in 4-week-old BALB/c, C.C3-H2(k)/LiMcdJ, an d DBA/2 mice as in Swiss/ICR mice. But it was more pathogenic for C57BL/6 m ice, and highly virulent for C3H/Hej and C3H/Hen mice, demonstrating the im portance of murine genotype, sis expected from its virulence in all mouse s trains, vMwt, with a poly(C) of C44UC10, induced higher levels of viremia t han vMC(24). The vMwt also induced higher levels of circulating interferon and had reduced pathogenicity in chemically immunosuppressed Swiss/ICR mice . Similar immunosuppression did not increase the virulence of vMC(24). Coll ectively, the data suggest that endogenous immune components and the immune competence of the host play significant roles in determining the susceptib ility of mice to mengovirus infection.