Ausschuss für Hygiene

Lactate Dehydrogenase Elevating Virus

Host species:
  • mouse (Mus musculus, Mus caroli) (Rowsan 1980)

Organotropism:
  • polytropic strains: liver, spleen, lymphnodes, testistissue
  • neurovirulant strain: LDV-C: central nervous system, anterior horn neurons leptominges
  • mucosal barrier to viral transmission

Clinical disease:
  • life long asymptomatic, low level viremic persistence
  • immunosuppressed AKR and C58 strain: poliomyelitis with fatal paralysis
  • mice are infected by mechanical transfer of tissues or serum from infected animals
  • natural transmission between cagemates is rare

Morbidity and mortality
  • morbidity and mortality are very low
  • morbidity and mortality depend on host strain, immunodeficiency and presence of murine retro viruses

Zoonotic potencial
  • none

Importent notice:
  • Detection of LDV: measuring LDH levels in mouse plasma PCR-assay ( van der Logt et al 1994)

Interference with research:

Oncology

  • enhancement of tumor growth (Mc. Donald 1983, Isakov and Feldmann 1981)
  • suppression of chemically induced mouse lung tumorigenesis (Theiss et al 1980) and foreign body tumorigenesis (Brinton-Darnell-M 1977)
  • Contamination of transplantable tumors (Nicklas et al 1993, Isakov et al 1981, Riley et al 1978)
  • interactions with oncogene murine retro viruses: ecotropic murine leukemia virus (Anderson et al 1995, Inada et al 1993, Inada 1993, Inada et Yamazaki 1991, Contag and Plagemann 1989, Contag and Plagemann 1988)

Infectiology

  • impaired resistance to bacterial infection (Bonventre et al 1980)

Immunology

  • stimulation of B-lymphocyte-activation (Bradley et al 1991, Coutelier et al 1990) and systemic alteration in lymphocyte circulatory pattern (Mongini 1978)
  • elevation of immunoglobulin isotype blood levels IgG2a (Hovinen et al 1990, Li et al 1990, Coutelier et al 1986, Coutelier and Van Snick 1985, Cafruny and Plagemann 1982)
  • contaminant of monoclonal antibodies (Nicklas et al 1988)
  • induction of interferon production (Lussenhop et al 1982, Nicklas et al 1988, Koi et al 1981, Evans and Riley 1968, Lagwinska et al 1975)
  • influence on immunogenic function of macrophages and macrophage-dependent immunresponse (Isakov at al 1982, Ritzi et al 1982)
  • enhancement of natural killer cell activity (Koi et al 1981) and elevation of cytooxic T-lymphocytes (Even et al 1995)
  • reduction of autoantibody production (Verdonck et al 1994, Hayashi et al 1992)
  • suppression of cell mediated immunresponses; inhibition of cytokine production IL-4, IL-1 (Monteyne et al 1993, Hayashi et al 1991)

Physiology

  • changes in hemopoiesis after tumortransplantation (Motycka et al 1981, Viktora et al 1981)
  • suppression of development of glomerulonephritis in autoimmune NZB-mice (Kameyama and Hayashi 1994, Hayashi et al 1993)
  • decrease of incidence of diabetes in NOD-mice (Takei et al 1992) and reduction of streptozotocin-induced diabetis mellitus in CD-1-mice (Hayashi et al 1994)
  • changes in clearance capacity for several enzymes and proteins (Winkelhake et al 1978, Hayashi et al 1988, Hayashi et al 1992, Nakayama et al 1990, Brinton et Plagemann 1983)
  • increase of serum lactate dehydrogenase level and other enzymes (Brinton 1982)
  • mucosal barrier to LDV transmission exists (Cafruny and Hovinen 1988, Cafruny et al 1991, Broen et al 1992)

References:

Anderson, G. W., G. A. Palmer, R. R. Rowland, C. Even, and P. G. Plagemann. 1995. Infection of central nervous system cells by ecotropic murine leukemia virus in C58 and AKR mice and in in utero-infected CE/J mice predisposes mice to paralytic infection by lactate dehydrogenase-elevating virus. J. Virol. 69:308-319.

Bonventre, P. F., H. C. Bubel, J. G. Michael, and A. D. Nickol. 1980. Impaired resistance to bacterial infection after tumor implant is traced to lactic dehydrogenase virus. Infect. Immun. 30:316-319.

Bradley, D. S., J. J. Broen, and W. A. Cafruny. 1991. Infection of SCID mice with lactate dehydrogenase-elevating virus stimulates B-cell activation. Viral Immunol. 4:59-70.

Brinton, M. A., M. Darnell, and I. Brand. 1977. Delayed foreign-body tumorigenesis in mice infected with lactate dehydrogenase-elevating virus: Brief communication. J. Natl. Cancer Inst. 59:1027-1029.

Brinton, M. A. Lactate dehydrogenase-elevating virus. In „The Mouse in Biomedical Research (H. L. Foster, J. D. Small, and L. G. Fox, eds.), Vol. 2, p.194. Academic Press 1982; New York.

Brinton, M. A., P. G. Plagemann. 1983. Clearance of lactate dehydrogenase by SJL/J mice infected with lactate dehydrogenase-elevating virus. J. Reticuloendothel Soc. 33:391-400.

Broen, J. J., S. E. DesJarlais, R. G. Duman, S. N. Anderson, R. A. Mueller, W. A. Cafruny. 1992. Virucidal effect of murine duodenal extracts: studies with lactate dehydrogenase-elevating virus. Antiviral Res. 18:327-340.

Cafruny, W. A., and P. G. Plagemann. 1982. Immune response to lactate dehydrogenase-elevating virus: isolation of infectious virus-immunoglobulin G complexes and quantitation of specific antiviral immuno-globulin G response in wild-type and nude mice. Infect. Immun. 37:1001-1006.

Cafruny, W. A., D. E. Hovinen. 1988. The relationship between route of infection and minimum infectious dose: studies with lactate dehydrogenase-elevating virus. J. Virol. Methods. 20:265-268.

Cafruny, W. A. 1989. Lactate dehydrogenase-elevating virus: biology and pathogenesis. Crit. Rev. Microbiol. 17:107-119.

Cafruny, W. A., S. E. DesJarlais, M. L. Hecht, J. J. Broen, and R. A. Jaqua. 1991. Enhancement of murine susceptibility to oral lactate dehydrogenase-elevating virus infection by non-steroidal anti-inflammatory agents, and antagonism by misoprostol. Antiviral Res. 15:77-83.

Contag, C. H., and P. G. Plagemann. 1988. Susceptibility of C58 mice to paralytic disease induced by lactate dehydrogenase-elevating virus correlates with increased expression of endogenous retrovirus in motor neurons. Microb. Pathog. 5:287-296.

Contag, C. H., and P. G. Plagemann. 1989. Age-dependent poliomyelitis of mice: expression of endogenous retrovirus correlates with cytocidal replication of lactate dehydrogenase-elevating virus in motor neurons. J. Virol. 63:4362-4369.

Coutelier, J. P., and J. Van-Snick. 1985. Isotypically restricted activation of B lymphocytes by lactic dehydrogenase virus. Eur. J. Immunol. 15:250-255.

Coutelier, J. P., E. Van-Roost, P. Lambotte, and J. Van-Snick. 1986. The murine antibody response to lactate dehydrogenase-elevating virus. J. Gen. Virol. 67:1099-1108.

Coutelier, J. P., P.G. Coulie, P. Wauters, H. Heremans, and J. T. van-der-Logt. 1990. In vivo polyclonal B-lymphocyte activation elicited by murine viruses. J. Virol. 64:5383-5388.

Evans, R., and V. Riley. 1968. Circulating interferon in mice infected with the lactate dehydrogenase-elevating virus. J. Gen. Virol. 3:449-452.

Even, C., R. R. Rowland, and P. G. Plagemann. 1995. Cytotoxic T cells are elicited during acute infection of mice with lactate dehydrogenase-elevating virus but disappear during the chronic phase of infection. J. Virol. 69:5666-5676.

Hayashi, T., K. Salata, A. Kingman, A.L. Notkins. 1988. Regulation of enzyme levels in the blood. Influence of environmental and genetic factors on enzyme clearance. Am. J. Pathol. 132:503-511.

Hayashi, T., H. Iwata, T. Hasegawa, M. Ozaki, H. Yamamoto, and T. Onodera. 1991. Decrease in neutrophil migration induced by endotoxin and suppression of interleukin-1 production by macrophages in lactic dehydrogenase virus-infected mice. J. Comp. Pathol. 104:161-170.

Hayashi, T., M. Ozaki, I. Mori, M. Saito, T. Itoh, and H. Yamamoto. 1992. Enhanced clearance of lactic dehydrogenase-5 in severe combined immunodeficiency (SCID) mice: effect of lactic dehydrogenase virus on enzyme clearance. Int. J. Exp. Pathol. 73:173-181.

Hayashi, T. 1992. Effect of prostaglandin E2 on plasma lactic dehydrogenase activity in (NZB x NZW)F1 mice with a chronic infection of lactic dehydrogenase virus. J. Comp. Pathol. 107:41-48.

Hayashi, T., I. Mori, and H. Yamamoto. 1992. Lactic dehydrogenase virus infection prevents development of anti-nuclear antibody in (NZB x NZW)F1 mice; role of prostaglandin E2 and macrophage Ia antigen expression. Int. J. Exp. Pathol. 73:593-601.

Hayashi, T., Y. Noguchi, and Y. Kameyama. 1993. Suppression of development of anti-nuclear antibody and glomerulonephritis in NZB x NZWF1 mice by persistent infection with lactic dehydrogenase virus: possible involvement of superoxide as a progressive effector. Int. J. Exp. Pathol. 74:553-560.

Hayashi, T., S. Hashimoto, and Y. Kameyama. 1994. Reduced streptozotocin-induced insulitis in CD-1 mice by treatment with anti-intercellular adhesion molecule-1 and anti-lymphocyte function associated antigen-1 monoclonal antibodies together with lactic dehydrogenase virus infection. Int. J. Exp. Pathol. 75:117-121.

Hayashi, T., S. Hashimoto, and A. Kawashima. 1994. Effect of infection by lactic dehydrogenase virus on expression of intercellular adhesion molecule-1 on vascular endothelial cells of pancreatic islets in streptozotocin-induced insulitis of CD-1 mice. Int. J. Exp. Pathol. 75:211-217.

Hovinen, D. E., D. S. Bradley, and W. A. Cafruny. 1990. Analysis of immunoglobulin isotype blood levels, splenic B-cell phenotypes, and spleen cell immunoglobulin gene expression in mice infected with lactate dehydrogenase-elevating virus. Viral. Immunol. 3:27-40.

Inada, T. 1993. Replication of lactate dehydrogenase-elevating virus in various species cell lines infected with dual-, ampho- and xenotropic murine leukaemia viruses in vitro. Virus Res. 27:267-281.

Inada, T., H. Kikuchi, and S. Yamazaki. 1993. Comparison of the ability of lactate dehydrogenase-elevating virus and its virion RNA to infect murine leukemia virus-infected or -uninfected cell lines. J. Virol. 67:5698-5703.

Isakov, N., M. Feldman, and S. Segal. 1981. Effect of lactic dehydrogenase virus infection on tumor induction and tumor growth. Cancer Res. 41:667-672.

Isakov, N., S. Segal, and M. Feldman. 1981. The immunoregulatory characteristics of the lactic dehydrogenase virus (LDV), a common contaminant of tumors. Cell. Mol. Biol. 27:83-96.

Isakov, N., M. Feldman, and S. Segal. 1982. Lactic dehydrogenase virus (LDV) impairs the antigen-presenting capacity of macrophages yet fails to affect their phagocytic activity. Immunobiology 162:15-27.

Kameyama, Y., and T. Hayashi. 1994. Suppression of development of glomerulonephritis in NZB x NZWF1 mice by persistent infection with lactic dehydrogenase virus: relations between intercellular adhesion molecule-1 expression on endothelial cells and leucocyte accumulation in glomeruli. Int. J. Exp. Pathol. 75:295-304.

Koi, M., M. Saito, T. Ebina, and N. Ishida. 1981. Lactate dehydrogenase-elevating agent is responsible for interferon induction and enhancement of natural killer cell activity by inoculation of Ehrlich ascites carcinoma cells into mice. Microbiol. Immunol. 25:565-574.

Lagwinska, E., C. C. Stewart, C. Adles, and S. Schlesinger. 1975. Replication of lactic dehydrogenase virus and Sindbis virus in mouse peritoneal macrophages. Induction of interferon and phenotypic mixing. Virology 65:204-214

Li, X., B. Hu, J. Harty, C. Even, and P. G. Plagemann. 1990. Polyclonal B cell activation of IgG2a and IgG2b production by infection of mice with lactate dehydrogenase-elevating virus is partly dependent on CD4+ lymphocytes. Viral Immunol. 3:273-288.

Lussenhop, N., B. Holmes, W. A. Cafruny, and P. G. Plagemann. 1982. Acute infection of mice with lactate dehydrogenase-elevating virus enhances Fc and complement receptor activity of peritoneal macrophages. J. Gen. Virol. 61:25-32.

McDonald, T. L. 1983. Blocking of cell-mediated immunity to Moloney murine sarcoma virus-transformed cells by lactate dehydrogenase virus-antibody complex. J. Natl. Cancer Inst. 70:493-497.

Mongini, P. K., and L. T. Rosenberg. 1978. Lactic dehydrogenase virus alteration of lymphocyte circulation. J. Immunol. 120:459-462.

Motycka, K., A. Balcarova, A. Pezlarova, and A. Jandova. 1981. Changes in hemopoiesis of mice of the C3H strain following transplantation of Gardner lymphosarcoma and infection with LDH-virus. III. Blood proteins. Neoplasma 28:95-102.

Monteyne, P., J. Van-Broeck, J. Van-Snick, and J. P. Coutelier. 1993. Inhibition by lactate dehydrogenase-elevating virus of in vivo interleukin 4 production during immunization with keyhole limpet haemocyanin. Cytokine 5:394-397.

Nakayama, H., T. Hayashi, K. F. Salata, and A. L. Notkins. 1990. Flow cytometry to identify cell types to which enzymes bind. Effect of lactic dehydrogenase virus on enzyme binding. J. Biol. Chem. 265:14355-14357.

Nicklas, W., M. Giese, R. Zawatzky, H. Kirchner, and P. Eaton. 1988. Contamination of a monoclonal antibody with LDH-virus causes interferon induction. Lab. Anim. Sci. 38:152-154.

Nicklas, W., V. Kraft, and B. Meyer. 1993. Contamination of transplantable tumors, cell lines, and monaclonal antibodies with rodent virus. Lab. Anim. Sci. 43:296-300.

Riley, V., D. H. Spackman, G. A. Santisteban, G. Dalldorf, I. Hellstrom, K. E. Hellstrom, E. M. Lance, K. E. Rowson, B. W. Mahy, P. Alexander, C. C. Stock, H. O. Sjogren, V. P. Hollander, and M. C. Horzinek. 1978. The LDH virus: an interfering biological contaminant. Science 200:124-126.

Ritzi, D. M., M. Holth, M. S. Smith, W. J. Swart, W. A. Cafruny, G. W. Plagemann, and J. A. Stueckemann. 1982. Replication of lactate dehydrogenase-elevating virus in macrophages. 1. Evidence for cytocidal replication. J. Gen. Virol. 59:245-262.

Rowson, K. E. 1980. A new host species for lactic dehydrogenase virus. Experientia 36:1066-1067.

Takei, I., Y. Asaba, T. Kasatani, T. Maruyama, K. Watanabe, T. Yanagawa, T. Saruta, and T. Ishii. 1992. Suppression of development of diabetes in NOD mice by lactate dehydrogenase virus infection. J. Autoimmun. 5:665-673

Theiss, J. C., M. B. Shimkin, G. D. Stoner, A. J. Kniazeff, and R. D. Hoppenstand. 1980. Effect of lactate dehydrogenase virus on chemically induced mouse lung tumorigenesis. Cancer Res. 40:64-66.

van der Logt, J. T., J. Kissing, and W. J. Melchers. 1994. Enzymatic amplification of lactate dehydrogenase-elevating virus. J. Clin. Microbiol. 32:2003-2006.

Verdonck, E., C. J. Pfau, M. D. Gonzalez, P. L. Masson, and J. P. Coutelier. 1994. Influence of viral infection on anti-erythrocyte autoantibody response after immunization of mice with rat red blood cells. Autoimmunity 17:73-81.

Viktoria, L., K. Motycka, A. Jirasek, A. Balcarova, and K. Neuwirtova. 1981. Changes in hemopoiesis of mice of the C3H strain following transplantation of Gardner lymphosarcoma and infection with LDH-virus. II. Spleen and bone marrow. Neoplasma 28:87-93.

Winkelhake, J. L., B. M. Elcombe, and R.J. Chang. 1978. Protracted circulating lifetimes of mannose-terminated glycoproteins and aggregated albumin in mice infected with LDH-elevating virus. Physiol. Chem. Phys. 10:305-322.
Author: Karin Jacobi, Max-Delbrück-Centrum Berlin-Buch, Germany