Transformation of Rabbit Vascular Smooth Muscle Cells by Human Cytomegalovirus Morphological Transforming Region I

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 1997 Nov 14

PMID 9358765

Citations 1

Authors

A Legrand

E P Mayer

S S Dalvi

M Nachtigal

Affiliations

Soon will be listed here.

Abstract

The association of human cytomegalovirus with atherosclerosis and the monoclonal hypothesis of atherogenesis suggested that transformation of vascular smooth muscle cells may be an outcome of the virus-host cell interaction. To test this hypothesis, rabbit aorta smooth muscle cells were transfected with the morphological transforming region I (mtrI) of human cytomegalovirus (HCMV) linked to the neomycin resistance gene. Foci of neomycin-resistant and morphologically transformed cells were isolated and expanded into fourteen RCMV strains. Eight of these strains acquired immortalization, but only one strain (RCMV-21) retained recombined viral sequences integrated in the cellular DNA. RCMV strains were heterogeneous in their morphology, expression of smooth muscle alpha-actin, growth, and mitogenic response to serum and fibroblast growth factor (FGF)-2 and -4. All RCMV strains assayed except RCMV-3 showed DNA synthesis in low serum medium and, with the exception of RCMV-1 cells, all showed a significant mitogenic response to FGF-2 and FGF-4, Maintenance of the transformed phenotype appeared independent of the retention of the transforming viral sequences, which was suggestive of a "hit-and-run" mechanism. These results suggested that morphological transformation by HCMV DNA sequences could enhance the mitogenic response of vascular smooth muscle cells to fibroblast growth factors.

Citing Articles

The relationship between human cytomegalovirus infection and atherosclerosis development.

Chen R, Xiong S, Yang Y, Fu W, Wang Y, Ge J Mol Cell Biochem. 2003; 249(1-2):91-6.

PMID: 12956403

References

McDonald K, Rector T, Braulin E, Kubo S, Olivari M . Association of coronary artery disease in cardiac transplant recipients with cytomegalovirus infection. Am J Cardiol. 1989; 64(5):359-62. DOI: 10.1016/0002-9149(89)90535-3. View

Nachtigal M, Nagpal M, Greenspan P, Nachtigal S, Legrand A . Characterization of a continuous smooth muscle cell line derived from rabbit aorta. In Vitro Cell Dev Biol. 1989; 25(10):892-8. DOI: 10.1007/BF02624001. View

Hendrix M, Salimans M, van Boven C, Bruggeman C . High prevalence of latently present cytomegalovirus in arterial walls of patients suffering from grade III atherosclerosis. Am J Pathol. 1990; 136(1):23-8. PMC: 1877468. View

Galloway D, McDougall J . Alterations in the cellular phenotype induced by herpes simplex viruses. J Med Virol. 1990; 31(1):36-42. DOI: 10.1002/jmv.1890310108. View

Lindner V, Lappi D, Baird A, Majack R, Reidy M . Role of basic fibroblast growth factor in vascular lesion formation. Circ Res. 1991; 68(1):106-13. DOI: 10.1161/01.res.68.1.106. View

Talarico D, Basilico C . The K-fgf/hst oncogene induces transformation through an autocrine mechanism that requires extracellular stimulation of the mitogenic pathway. Mol Cell Biol. 1991; 11(2):1138-45. PMC: 359796. DOI: 10.1128/mcb.11.2.1138-1145.1991. View

Armstrong M, Heistad D . Animal models of atherosclerosis. Atherosclerosis. 1990; 85(1):15-23. DOI: 10.1016/0021-9150(90)90178-l. View

Hendrix M, Daemen M, Bruggeman C . Cytomegalovirus nucleic acid distribution within the human vascular tree. Am J Pathol. 1991; 138(3):563-7. PMC: 1886290. View

Legrand A, Greenspan P, Nagpal M, Nachtigal S, Nachtigal M . Characterization of human vascular smooth muscle cells transformed by the early genetic region of SV40 virus. Am J Pathol. 1991; 139(3):629-40. PMC: 1886216. View

10.

Hajjar D . Warner-Lambert/Parke-Davis Award Lecture. Viral pathogenesis of atherosclerosis. Impact of molecular mimicry and viral genes. Am J Pathol. 1991; 139(6):1195-211. PMC: 1886453. View

11.

STARY H, Blankenhorn D, Chandler A, Glagov S, INSULL Jr W, Richardson M . A definition of the intima of human arteries and of its atherosclerosis-prone regions. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1992; 85(1):391-405. DOI: 10.1161/01.cir.85.1.391. View

12.

Halbert C, Smith P, BENDITT E, McDougall J . Immortalization of primary human smooth muscle cells. Proc Natl Acad Sci U S A. 1992; 89(4):1224-8. PMC: 48421. DOI: 10.1073/pnas.89.4.1224. View

13.

Wu T, Hruban R, Ambinder R, Pizzorno M, CAMERON D, Baumgartner W . Demonstration of cytomegalovirus nucleic acids in the coronary arteries of transplanted hearts. Am J Pathol. 1992; 140(3):739-47. PMC: 1886167. View

14.

Mansukhani A, DellEra P, Moscatelli D, Kornbluth S, Hanafusa H, Basilico C . Characterization of the murine BEK fibroblast growth factor (FGF) receptor: activation by three members of the FGF family and requirement for heparin. Proc Natl Acad Sci U S A. 1992; 89(8):3305-9. PMC: 48855. DOI: 10.1073/pnas.89.8.3305. View

15.

Bauer G, Kahl S, Sawhney I, Hofler P, Gerspach R, Matz B . Transformation of rodent fibroblasts by herpes simplex virus: presence of morphological transforming region 1 (MTR 1) is not required for the maintenance of the transformed state. Int J Cancer. 1992; 51(5):754-60. DOI: 10.1002/ijc.2910510515. View

16.

Ross R . The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362(6423):801-9. DOI: 10.1038/362801a0. View

17.

Winkles J, Friesel R, Alberts G, Janat M, Liau G . Elevated expression of basic fibroblast growth factor in an immortalized rabbit smooth muscle cell line. Am J Pathol. 1993; 143(2):518-27. PMC: 1887007. View

18.

Lemstrom K, Bruning J, Bruggeman C, Lautenschlager I, Hayry P . Cytomegalovirus infection enhances smooth muscle cell proliferation and intimal thickening of rat aortic allografts. J Clin Invest. 1993; 92(2):549-58. PMC: 294886. DOI: 10.1172/JCI116622. View

19.

Hughes S, Crossman D, Hall P . Expression of basic and acidic fibroblast growth factors and their receptor in normal and atherosclerotic human arteries. Cardiovasc Res. 1993; 27(7):1214-9. DOI: 10.1093/cvr/27.7.1214. View

20.

Koskinen P, Lemstrom K, Bruggeman C, Lautenschlager I, Hayry P . Acute cytomegalovirus infection induces a subendothelial inflammation (endothelialitis) in the allograft vascular wall. A possible linkage with enhanced allograft arteriosclerosis. Am J Pathol. 1994; 144(1):41-50. PMC: 1887122. View