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. 1993 May 2;121(4):785–793. doi: 10.1083/jcb.121.4.785

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

PMCID: PMC2119794  PMID: 8491772

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 approximately 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 approximately 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.

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Selected References

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  1. Alonso S., Minty A., Bourlet Y., Buckingham M. Comparison of three actin-coding sequences in the mouse; evolutionary relationships between the actin genes of warm-blooded vertebrates. J Mol Evol. 1986;23(1):11–22. doi: 10.1007/BF02100994. [DOI] [PubMed] [Google Scholar]
  2. Baruch A. M., Despommier D. D. Blood vessels in Trichinella spiralis infections: a study using vascular casts. J Parasitol. 1991 Feb;77(1):99–103. [PubMed] [Google Scholar]
  3. Benezra R., Davis R. L., Lockshon D., Turner D. L., Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. doi: 10.1016/0092-8674(90)90214-y. [DOI] [PubMed] [Google Scholar]
  4. Buskin J. N., Jaynes J. B., Chamberlain J. S., Hauschka S. D. The mouse muscle creatine kinase cDNA and deduced amino acid sequences: comparison to evolutionarily related enzymes. J Mol Evol. 1985;22(4):334–341. doi: 10.1007/BF02115689. [DOI] [PubMed] [Google Scholar]
  5. Carlson B. M., Faulkner J. A. The regeneration of skeletal muscle fibers following injury: a review. Med Sci Sports Exerc. 1983;15(3):187–198. [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Connolly J. A., Kiosses B. W., Kalnins V. I. Centrioles are lost as embryonic myoblasts fuse into myotubes in vitro. Eur J Cell Biol. 1986 Jan;39(2):341–345. [PubMed] [Google Scholar]
  8. Cossu G., Eusebi F., Grassi F., Wanke E. Acetylcholine receptor channels are present in undifferentiated satellite cells but not in embryonic myoblasts in culture. Dev Biol. 1987 Sep;123(1):43–50. doi: 10.1016/0012-1606(87)90425-8. [DOI] [PubMed] [Google Scholar]
  9. Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
  10. Despommier D. D., Gold A. M., Buck S. W., Capo V., Silberstein D. Trichinella spiralis: secreted antigen of the infective L1 larva localizes to the cytoplasm and nucleoplasm of infected host cells. Exp Parasitol. 1990 Jul;71(1):27–38. doi: 10.1016/0014-4894(90)90005-w. [DOI] [PubMed] [Google Scholar]
  11. Despommier D. Adaptive changes in muscle fibers infected with Trichinella spiralis. Am J Pathol. 1975 Mar;78(3):477–496. [PMC free article] [PubMed] [Google Scholar]
  12. Despommier D., Aron L., Turgeon L. Trichinella spiralis: growth of the intracellular (muscle) larva. Exp Parasitol. 1975 Feb;37(1):108–116. doi: 10.1016/0014-4894(75)90058-2. [DOI] [PubMed] [Google Scholar]
  13. Despommier D., Symmans W. F., Dell R. Changes in nurse cell nuclei during synchronous infection with Trichinella spiralis. J Parasitol. 1991 Apr;77(2):290–295. [PubMed] [Google Scholar]
  14. Edmondson D. G., Olson E. N. A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program. Genes Dev. 1989 May;3(5):628–640. doi: 10.1101/gad.3.5.628. [DOI] [PubMed] [Google Scholar]
  15. Fanning E. Simian virus 40 large T antigen: the puzzle, the pieces, and the emerging picture. J Virol. 1992 Mar;66(3):1289–1293. doi: 10.1128/jvi.66.3.1289-1293.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Feagin J. E., Jasmer D. P., Stuart K. Developmentally regulated addition of nucleotides within apocytochrome b transcripts in Trypanosoma brucei. Cell. 1987 May 8;49(3):337–345. doi: 10.1016/0092-8674(87)90286-8. [DOI] [PubMed] [Google Scholar]
  17. Fogel M., Defendi V. Infection of muscle cultures from various species with oncogenic DNA viruses (SV40 and polyoma). Proc Natl Acad Sci U S A. 1967 Sep;58(3):967–973. doi: 10.1073/pnas.58.3.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gabryel P., Gustowska L. Veränderungen der quergestreiften Muskelfasern im frühen Stadium einer Trichinella spiralis-Infektion. Gegenbaurs Morphol Jahrb. 1967;111(2):174–180. [PubMed] [Google Scholar]
  19. Galili G., Kawata E. E., Cuellar R. E., Smith L. D., Larkins B. A. Synthetic oligonucleotide tails inhibit in vitro and in vivo translation of SP6 transcripts of maize zein cDNA clones. Nucleic Acids Res. 1986 Feb 11;14(3):1511–1524. doi: 10.1093/nar/14.3.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Graessmann A., Graessmann M., Fogel M. The relationship of polyoma virus-induced tumor (T) antigen to activation of DNA synthesis in rat myotubes. Dev Biol. 1973 Nov;35(1):180–186. doi: 10.1016/0012-1606(73)90016-x. [DOI] [PubMed] [Google Scholar]
  21. Grounds M. D., McGeachie J. K. Reutilisation of tritiated thymidine in studies of regenerating skeletal muscle. Cell Tissue Res. 1987 Oct;250(1):141–148. doi: 10.1007/BF00214665. [DOI] [PubMed] [Google Scholar]
  22. Iujvidin S., Fuchs O., Nudel U., Yaffe D. SV40 immortalizes myogenic cells: DNA synthesis and mitosis in differentiating myotubes. Differentiation. 1990 Jun;43(3):192–203. doi: 10.1111/j.1432-0436.1990.tb00446.x. [DOI] [PubMed] [Google Scholar]
  23. Jasmer D. P., Bohnet S., Prieur D. J. Trichinella spp.: differential expression of acid phosphatase and myofibrillar proteins in infected muscle cells. Exp Parasitol. 1991 Apr;72(3):321–331. doi: 10.1016/0014-4894(91)90152-m. [DOI] [PubMed] [Google Scholar]
  24. Jasmer D. P., Feagin J. E., Stuart K. Diverse patterns of expression of the cytochrome c oxidase subunit I gene and unassigned reading frames 4 and 5 during the life cycle of Trypanosoma brucei. Mol Cell Biol. 1985 Nov;5(11):3041–3047. doi: 10.1128/mcb.5.11.3041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jasmer D. P. Trichinella spiralis: altered expression of muscle proteins in trichinosis. Exp Parasitol. 1990 May;70(4):452–465. doi: 10.1016/0014-4894(90)90130-5. [DOI] [PubMed] [Google Scholar]
  26. Lassar A. B., Thayer M. J., Overell R. W., Weintraub H. Transformation by activated ras or fos prevents myogenesis by inhibiting expression of MyoD1. Cell. 1989 Aug 25;58(4):659–667. doi: 10.1016/0092-8674(89)90101-3. [DOI] [PubMed] [Google Scholar]
  27. Lee H. H., Kaighn M. E., Ebert J. D. Induction of thymidine-3H incorporation in multinucleated myotubes by Rous sarcoma virus. Int J Cancer. 1968 Jan 15;3(1):126–136. doi: 10.1002/ijc.2910030115. [DOI] [PubMed] [Google Scholar]
  28. Li L., Hu J. S., Olson E. N. Different members of the jun proto-oncogene family exhibit distinct patterns of expression in response to type beta transforming growth factor. J Biol Chem. 1990 Jan 25;265(3):1556–1562. [PubMed] [Google Scholar]
  29. Maeir D. M., Zaiman H. The development of lysosomes in rat skeletal muscle in trichinous myositis. J Histochem Cytochem. 1966 May;14(5):396–400. doi: 10.1177/14.5.396. [DOI] [PubMed] [Google Scholar]
  30. Maniotis A., Schliwa M. Microsurgical removal of centrosomes blocks cell reproduction and centriole generation in BSC-1 cells. Cell. 1991 Nov 1;67(3):495–504. doi: 10.1016/0092-8674(91)90524-3. [DOI] [PubMed] [Google Scholar]
  31. Reznik M. Influence d'une irradiation locale unique sur le muscle strié en régénération. Arch Biol (Liege) 1967;78(1):91–106. [PubMed] [Google Scholar]
  32. Snow M. H. An autoradiographic study of satellite cell differentiation into regenerating myotubes following transplantation of muscles in young rats. Cell Tissue Res. 1978 Jan 31;186(3):535–540. doi: 10.1007/BF00224941. [DOI] [PubMed] [Google Scholar]
  33. Snow M. H. Myogenic cell formation in regenerating rat skeletal muscle injured by mincing. II. An autoradiographic study. Anat Rec. 1977 Jun;188(2):201–217. doi: 10.1002/ar.1091880206. [DOI] [PubMed] [Google Scholar]
  34. Tassin A. M., Maro B., Bornens M. Fate of microtubule-organizing centers during myogenesis in vitro. J Cell Biol. 1985 Jan;100(1):35–46. doi: 10.1083/jcb.100.1.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Teppema J. S., Robinson J. E., Ruitenberg E. J. Ultrastructural aspects of capsule formation in Trichinella spiralis infection in the rat. Parasitology. 1973 Apr;66(2):291–296. doi: 10.1017/s0031182000045224. [DOI] [PubMed] [Google Scholar]
  36. Weydert A., Daubas P., Caravatti M., Minty A., Bugaisky G., Cohen A., Robert B., Buckingham M. Sequential accumulation of mRNAs encoding different myosin heavy chain isoforms during skeletal muscle development in vivo detected with a recombinant plasmid identified as coding for an adult fast myosin heavy chain from mouse skeletal muscle. J Biol Chem. 1983 Nov 25;258(22):13867–13874. [PubMed] [Google Scholar]
  37. Yaffe D., Gershon D. Multinucleated muscle fibres: induction of DNA synthesis and mitosis by polyoma virus infection. Nature. 1967 Jul 22;215(5099):421–424. doi: 10.1038/215421a0. [DOI] [PubMed] [Google Scholar]

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