Trichinella spiralis infected skeletal muscle cells arrest in G2/M and cease muscle gene expression

Abstract

Infection by Trichinella spiralis causes a variety of changes in skeletal muscle cells including the hypertrophy of nuclei and decreased expression of muscle specific proteins. Potential cellular processes leading to these changes were investigated. In synchronized muscle infections, [3H]thymidine was incorporated into infected cell nuclei from 2-5 days post infection. Labeled nuclei were stably integrated into the infected cell up to 60 days post infection and appear to originate from differentiated skeletal muscle nuclei present at the time of infection. These nuclei were further shown to contain a mean DNA content of ∼4N, indicating that the [3H]thymidine uptake reflects DNA synthesis and subsequent long-term suspension of the infected cell in the cell cycle at G2/M. Associated with these changes, muscle specific gene transcripts were reduced to <1-<0.1% in the infected cell compared to normal muscle. Transcript levels of the muscle transcriptional regulatory factors myogenin, MyoD1, and Id were reduced to <10, <1, and increased ∼250%, respectively, in the infected cell compared to normal muscle, indicating transcriptional inactivation of muscle genes. DNA synthesis in the infected cell may represent the initiation event which leads to expression of this infected cell phenotype.