Effect of oncogenic virus on muscle differentiation

Abstract

Chick muscle cultures infected with wild-type Rous sarcoma virus form myotubes, but these myotubes vacuolate and by day 6 most have degenerated, leaving only large numbers of transformed mononucleated, replicating cells. Muscle cultures infected with a temperature-sensitive mutant (TS) at permissive temperatures behave as cells infected with wild-type Rous sarcoma virus. TS-infected cells reared for 8 days at nonpermissive temperature form contracting myotubes, plus large numbers of fibroblastic cells. If these cultures are lowered to permissive temperature, within 72 hr the myotubes vacuolate and degenerate, whereas the mononucleated cells transform. If replicating TS-transformed cells after 8 days at permissive temperature are shifted to nonpermissive temperature, within 72 hr many cells fuse and form contracting, post-mitotic myotubes. Creatine kinase (ATP:creatine N-phosphotransferase, EC 2.7.3.2) levels parallel the formation and degeneration of myotubes during these temperature shifts. If the viral transforming gene is expressed in the post-mitotic myotubes it is lethal, whereas it is not lethal if expressed in replicating percursor myogenic cells. The viral gene expression at permissive temperature blocks further myogenesis depending on the position of the cells in the myogenic program. The virus does not cancel the replicating, transformed myogenic cells' commitment to, or position in, the myogenic lineage. When the transforming action of the virus is suppressed, the normal myogenic program resumes.