Ausschuss für Hygiene

MINUTE VIRUS OF MICE (MVM)

Host species:

  • natural host: laboratory and wild mice (Parker et al. 1970, Singleton et al. 1993, Smith et al. 1993)
  • hamsters and rats are susceptible to experimental infection (Kilham and Margolis 1970, 1971)

Properties of the Virus:

  • highly temperature resistant (Fassolitis et al. 1985)
  • highly resistant to environmental conditions like e.g. desiccation (Tattersall & Cotmore 1986, National Research Council 1991)
  • like other parvoviruses, MVM can infect cells only during the S phase of the mitotic cycle (Tattersall 1972)
  • two allotropic variants exist which replicate in fibroblasts (MVMp) or in T lymphocytes (MVMi) (McMaster et al. 1981, Spalholz and Tattersall 1983, Antonietti et al. 1988, Gardiner and Tattersall 1988)
  • Oncogenic transformation of cells by radiation, chemical carcinogens, or SV40 increases permissiveness to MVMp (Cornelis et al. 1988a).
  • transplacental transmission after experimental infection of pregnant hamsters, mice and rats (Kilham and Margolis 1971)
  • mouse embryos with intact zona pellucida are not susceptible to infection (Mohanty and Bachmann 1974)

Strain susceptibility:

  • the host strain may influence the mode and extend of horizontal transmission (Tattersall & Cotmore 1986)
  • three susceptibility phenotypes in response to MVMi: asymptomatic infection in C57BL/6, lethal with intestinal haemorrhage in DBA/2, lethal with renal haemorrhage in BALB/c, C3H and other strains (Brownstein et al. 1991)
  • amount of viral DNA produced during infection is dependent on host strain (Kapil 1995)

Organotropism:

  • viral replication only in mitotically active tissues like, e.g. embryos (Tattersall & Cotmore 1986)
  • benign foetal infections in mice (Kilham and Margolis 1975)
  • MVMi causes generalised infection of endothelium, lymphocytes, and haematopoietic cells and produces bilateral infarcts of the renal papilli (Brownstein et al. 1991)

Clinical disease:

  • natural infection of mice usually asymptomatic (Ward and Tattersall 1982, National Research Council 1991, Jacoby et al. 1996)
  • subclinical infection in experimentally infected rats or mice and lethal disease in hamsters after experimental infection (Kiham & Margolis 1970)
  • infectivity, organotropism, and pathogenesis of infection is dependent on characteristics of the virus (Brownstein et al. 1992, Jacoby & Ball-Goodrich 1995)
  • growth retardation of mice after experimental infection (Kilham and Margolis 1970)
  • MVMi but not MVMp is able to induce a runting syndrome in experimentally infected new-born mice (Kimsey et al. 1986)
  • foetal death and resorption (Kilham and Margolis 1971)
  • periodontal disease and mongolism in hamsters surviving experimental infection (Kilham and Margolis 1970)

Pathology:

  • intranuclear inclusions in some infected animals (Kilham and Margolis 1971)
  • no pathological lesions after natural infection (National Research Council 1991)

Morbidity and mortality:

  • MVMi more pathogenic for mice than MVMp, MVMi influences growth of mice shortly infected after birth, some die of the infection; non pathogenic in adult mice (Kimsey et al. 1986)
  • pathogenic in foetal hamsters and rats, no clinical disease in experimentally infeced mothers (Kilham and Margolis 1971)

Zoonotic potential:

  • none

Interference with research:

Pathology

  • intranuclear inclusion bodies (Kilham and Margolis 1971)
  • dental defects in aged hamsters after infection at 5 days of age (Baer and Kilham 1974)

Immunology

  • weak induction of interferon in vivo (Harris et al. 1974) and of IFN-b, TNFa and IL-6 in vitro (Schlehofer et al. 1992)
  • strong inhibitory effects of the immunosuppressive variant (MVMi) on allogeneic mixed lymphocyte cultures in vitro (Bonnard et al. 1976)
  • inhibition of lymphocyte proliferation and the generation of cytolytic T lymphocyte activity but not interferon production, inhibition of growth and cytolytic activity of T cell lines, suppression of an in vitro antibody response by MVMi but not by MVMp (Engers et al. 1981)
  • inhibition of the generation of cytolytic T lymphocytes by MVMi (McMaster et al. 1981)
  • reduction of T cell mitogenic responses and interference with helper dependent B cell responses in vitro (Tattersall and Cotmore 1986)
  • depression of splenic T cell and B cell mitogenic stimulation in vivo (Tattersall and Cotmore 1986)
  • neonatal infections by MVMi may have long-term effects on immunocompetence (Kimsey et al. 1986)
  • inhibition of haematopoiesis in vitro by MVMi but not by MVMp (Segovia et al. 1991, Bueren et al. 1991)
  • decreased haematopoiesis in spleen and bone marrow cells (Segovia et al. 1995)

Physiology

  • degeneration of the lens and the adjacent retinal layers after infection of new-born hamsters, extensive hypertrophy of the Harderian glands (Toolan 1983)

Cell biology

  • contaminant of cell lines, leukemias, and transplantable tumours (Parker et al. 1970, Collins and Parker 1972, Zoletto 1985, Garnick 1996, Chang et al. 1997)
  • persistent infection of cell lines (Ron & Tal 1985, Koering, C. E., et al. 1996)
  • disruption of nucleolar functions by virus replication in the nucleolus (Walton et al. 1989)
  • interference of a virus protein (NS1) with cell DNA replication, cell cycle stops in the S phase (op de Beeck & Caillet-Fauquet 1997)
  • viral DNA replication in fibroblasts co-infected with MVM and adenovirus is markedly dependent on the cell line (Fox et al. 1990)

Teratology

  • congenital malformation (Margolis & Kilham 1975)
  • death and resorption of foetuses (Kilham & Margolis 1971, Jordan & Sever 1994)

Infectiology

  • first described as a contaminant of a stock of mouse adenovirus (Crawford 1966)

Oncology

  • contamination of transplantable or chemically induced tumours (Parker et al. 1970, Collins & Parker 1972, Bonnard et al. 1976, Lussier 1991, Nicklas et al. 1993)
  • inhibition of cell transformation by SV40 (Mousset & Rommelaere 1982)
  • stable transformed phenotype is required for complete competence for MVM replication (Rommelaere & Tatersall 1990)
  • greater susceptibility of human oncogenic transformed cells and tumour-derived cell lines than of normal untransformed parental cells (Mousset et al. 1986, Cornelis et al. 1988a, Rommelaere & Cornelis 1991)
  • cultures of transformed rat fibroblasts are more susceptible to the cytopathic effect of MVMp than their untransformed homologues (Cornelis et al. 1988b, Guetta et al. 1990)
  • suppression of Ehrlich ascites tumours in mice after coinjection of MVM and acquisition of long-term resistance to additional injections of tumour cells (Guetta et al. 1986)
  • both strains suppress growth of p815 mastocytoma in mice concurrently infected (Kimsey et al. 1986)
  • oncogenes from different functional classes cooperate in the responsiveness of cells to attack by MVMp (Legrand et al. 1992)
  • cooperation of virus proteins (NS1) with oncogenes results in cell death (Mousset et al. 1994)

References:

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Baer, P. N., and L. Kilham. 1974. Dental defects in hamsters infected with Minute Virus of Mice. Oral Surg. 37:385-389.

Bonnard, G. D., E. K. Manders, D. A. Campbell, R. B. Herberman, and M. J. Collins. 1976. The immunosuppressive activity of a subline of the mouse EL-4 lymphoma. J. Exp. Med. 143:187-205.

Brownstein, D. G., A. L. Smith, R. O. Jacoby, E. A. Johnson, G. Hansen, and P. Tattersall. 1991. Pathogenesis of infection with a virulent allotropic variant of Minute Virus of Mice and regulation by host genotype. Lab. Invest. 65: 357-364.

Brownstein, D. G., A. L. Smith, E. A. Johnson, D. G. Pintel, L. K. Naeger, and P. Tattersall. 1992. The pathogenesis of infection with Minute Virus of Mice depends on the expression of the small nonstructural protein NS2 and on the genotype of the allotropic determinants VP1 and VP2. J. Virol. 66:3118-3124.

Bueren, J. A., J. C. Segovia, and J. M. Almendral. 1991. Cytotoxic infection of hematopoietic stem and committed progenitor cells by the parvovirus Minute Virus of Mice. Ann. N. Y. Acad. Sci. 628:262-272.

Chang, A., S. Havas, F. Borellini, J. Ostrove, and R. E. Bird. 1997. A rapid and simple procedure to detect the presence of MVM in conditioned cell fluids or culture media. Biologicals 25:415-419.

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Cornelis, J. J., P. Becquart, N. Duponchel, N. Salome, B. L. Avalosse, M. Namba, and J. Rommelaere. 1988a. Transformation of human fibroblasts by ionizing radiation, a chemical carcinogen, or simian virus 40 correlates with an increase in susceptibility to the autonomous parvoviruses H-1 virus and Minute Virus of Mice. J. Virol. 62:1679-1686.

Cornelis, J. J., N. Spruyt, P. Spegelaere, E.Guetta, T. Darawishi, S. F. Cotmore, J. Tal, and J. Rommelaere. 1988b. Sensitization of transformed rat fibroblasts to killing by parvovirus Minute Virus of Mice correlates with an increase in viral gene expression. J. Virol. 62:3438-3444.

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Guetta, E., M. Mincberg, S. Mousset, C. Bertinchamps, J. Rommelaers, and J. Tal. 1990. Selective killing of transformed rat cells by Minute Virus of Mice does not require infectious virus production. J. Virol. 64:458-462.

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Author: Werner Nicklas, DKFZ Heidelberg, Germany