Mengovirus and encephalomyocarditis virus poly(C) tract lengths can affectvirus growth in murine cell culture

Many virulent aphthoviruses and cardioviruses have long homopolymeric poly( C) tracts in the 5' untranslated regions of their RNA genomes, A panel of g enetically engineered mengo-type cardioviruses has been described which con tain a variety of different poly(C) tract lengths. Studies of these viruses have shown the poly(C) tract to be dispensable for grow-th in HeLa cells, although the relative murine virulence of the viruses correlates directly a nd positively with tract length, Compared with wild-type mengovirus strain M, mutants with shortened poly(C) tracts grow poorly in mice and protective ly immunize rather than kill recipient animals. In the present study, sever al murine cell populations were tested to determine whether, unlike HeLa ce lls, they allowed a differential amplification of viruses with long or shor t poly(C) tracts. Replication and cytopathic studies with four hematopoieti cally derived cell lines (CH2B, RAW 264.7, A20.J, and P815) and two murine fibroblast cell lines [L929 and L(Y)] demonstrated that several of these ce ll types indeed allowed differential virus replication as a function of vir al poly(C) tract length, Among the most discerning of these cells, RAW 264. 7 macrophages supported vigorous lytic growth of a long-tract virus, vMwt ( C44UC10), but supported only substantially diminished and virtually nonlyti c growth of vMC(24) (C13UC10) and vMC(0) short-tract viruses, The viral gro wth differences evident in all cell lines were apparent early and continuou sly during every cycle of virus amplification. The data suggest that poly(C ) tract-dependent attenuation of mengovirus may be due in part to a viral r eplication defect manifest in similar hematopoietic-type cells shortly afte r murine infection. The characterized cultures should provide excellent too ls for molecular study of poly(C) tract-mediated virulence.