Abstract
The genetic basis of the control of acute splenic MCMV infection was studied after intraperitoneal inoculation of the virus. Classical Mendelian analyses using C57BL/6 (resistant) and BALB/c (susceptible) parental strains disclosed an autosomal dominant non-H-2 gene that regulates splenic virus replication. The probable location of this gene, to which we have assigned the symbol Cmv-1, is on chromosome 6 as defined by the strain distribution pattern of splenic MCMV replication in CXB recombinant inbred mice. Although there is a similar hierarchy of resistance to MCMV and HSV-1 with respect to the C57BL and BALB genetic backgrounds, the strain distribution pattern of HSV-1 replication in recombinant inbred mice suggests that Cmv-1 is not involved in restricting the spread of this virus. This is the first clear identification of a non-H-2 gene regulating the magnitude of MCMV infection. Elucidation of the function of this gene may be a fundamental step towards understanding the control of systemic CMV infection.
Full Text
The Full Text of this article is available as a PDF (856.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allan J. E., Shellam G. R. Characterization of interferon induction in mice of resistant and susceptible strains during murine cytomegalovirus infection. J Gen Virol. 1985 May;66(Pt 5):1105–1112. doi: 10.1099/0022-1317-66-5-1105. [DOI] [PubMed] [Google Scholar]
- Allan J. E., Shellam G. R. Genetic control of murine cytomegalovirus infection: virus titres in resistant and susceptible strains of mice. Arch Virol. 1984;81(1-2):139–150. doi: 10.1007/BF01309303. [DOI] [PubMed] [Google Scholar]
- Allan J. E., Shellam G. R., Grundy J. E. Effect of murine cytomegalovirus infection on mitogen responses in genetically resistant and susceptible mice. Infect Immun. 1982 Apr;36(1):235–242. doi: 10.1128/iai.36.1.235-242.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Azen E. A., Davisson M. T., Cherry M., Taylor B. A. Prp (proline-rich protein) genes linked to markers Es-12 (esterase-12), Ea-10 (erythrocyte alloantigen), and loci on distal mouse chromosome 6. Genomics. 1989 Oct;5(3):415–422. doi: 10.1016/0888-7543(89)90004-9. [DOI] [PubMed] [Google Scholar]
- Bale J. F., Jr, O'Neil M. E., Giller R., Perlman S., Koszinowski U. Murine cytomegalovirus genomic material in marrow cells: relation to altered leukocyte counts during sublethal infection of mice. J Infect Dis. 1987 Feb;155(2):207–212. doi: 10.1093/infdis/155.2.207. [DOI] [PubMed] [Google Scholar]
- Bancroft G. J., Shellam G. R., Chalmer J. E. Genetic influences on the augmentation of natural killer (NK) cells during murine cytomegalovirus infection: correlation with patterns of resistance. J Immunol. 1981 Mar;126(3):988–994. [PubMed] [Google Scholar]
- Bukowski J. F., Woda B. A., Welsh R. M. Pathogenesis of murine cytomegalovirus infection in natural killer cell-depleted mice. J Virol. 1984 Oct;52(1):119–128. doi: 10.1128/jvi.52.1.119-128.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chalmer J. E., Mackenzie J. S., Stanley N. F. Resistance to murine cytomegalovirus linked to the major histocompatibility complex of the mouse. J Gen Virol. 1977 Oct;37(1):107–114. doi: 10.1099/0022-1317-37-1-107. [DOI] [PubMed] [Google Scholar]
- Cook M. L., Stevens J. G. Restricted replication of herpes simplex virus in spinal ganglia of resistant mice is accompanied by an early infiltration of immunoglobulin G-bearing cells. Infect Immun. 1983 May;40(2):752–758. doi: 10.1128/iai.40.2.752-758.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Field H. J., Bell S. E., Elion G. B., Nash A. A., Wildy P. Effect of acycloguanosine treatment of acute and latent herpes simplex infections in mice. Antimicrob Agents Chemother. 1979 Apr;15(4):554–561. doi: 10.1128/aac.15.4.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fuller J. L. Single-locus control of saccharin preference in mice. J Hered. 1974 Jan-Feb;65(1):33–36. doi: 10.1093/oxfordjournals.jhered.a108452. [DOI] [PubMed] [Google Scholar]
- Gresser I., Tovey M. G., Maury C., Bandu M. T. Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. II. Studies with herpes simplex, Moloney sarcoma, vesicular stomatitis, Newcastle disease, and influenza viruses. J Exp Med. 1976 Nov 2;144(5):1316–1323. doi: 10.1084/jem.144.5.1316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grundy J. E., Mackenzie J. S., Stanley N. F. Influence of H-2 and non-H-2 genes on resistance to murine cytomegalovirus infection. Infect Immun. 1981 Apr;32(1):277–286. doi: 10.1128/iai.32.1.277-286.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grundy J. E., Trapman J., Allan J. E., Shellam G. R., Melief C. J. Evidence for a protective role of interferon in resistance to murine cytomegalovirus and its control by non-H-2-linked genes. Infect Immun. 1982 Jul;37(1):143–150. doi: 10.1128/iai.37.1.143-150.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harnett G. B., Shellam G. R. Variation in murine cytomegalovirus replication in fibroblasts from different mouse strains in vitro: correlation with in vivo resistance. J Gen Virol. 1982 Sep;62(Pt 1):39–47. doi: 10.1099/0022-1317-62-1-39. [DOI] [PubMed] [Google Scholar]
- Katzenstein D. A., Yu G. S., Jordan M. C. Lethal infection with murine cytomegalovirus after early viral replication in the spleen. J Infect Dis. 1983 Sep;148(3):406–411. doi: 10.1093/infdis/148.3.406. [DOI] [PubMed] [Google Scholar]
- Lopez C. Genetics of natural resistance to herpesvirus infections in mice. Nature. 1975 Nov 13;258(5531):152–153. doi: 10.1038/258152a0. [DOI] [PubMed] [Google Scholar]
- Lopez C., Kirkpatrick D., Read S. E., Fitzgerald P. A., Pitt J., Pahwa S., Ching C. Y., Smithwick E. M. Correlation between low natural killing of fibroblasts infected with herpes simplex virus type 1 and susceptibility to herpesvirus infections. J Infect Dis. 1983 Jun;147(6):1030–1035. doi: 10.1093/infdis/147.6.1030. [DOI] [PubMed] [Google Scholar]
- Lopez C. Resistance to HSV-1 in the mouse is governed by two major, independently segregating, non-H-2 loci. Immunogenetics. 1980 Jul;11(1):87–92. doi: 10.1007/BF01567772. [DOI] [PubMed] [Google Scholar]
- Mercer J. A., Spector D. H. Pathogenesis of acute murine cytomegalovirus infection in resistant and susceptible strains of mice. J Virol. 1986 Feb;57(2):497–504. doi: 10.1128/jvi.57.2.497-504.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mims C. A., Gould J. Splenic necrosis in mice infected with cytomegalovirus. J Infect Dis. 1978 May;137(5):587–591. doi: 10.1093/infdis/137.5.587. [DOI] [PubMed] [Google Scholar]
- Nedrud J. G., Collier A. M., Pagano J. S. Cellular basis for susceptibility to mouse cytomegalovirus: evidence from tracheal organ culture. J Gen Virol. 1979 Dec;45(3):737–744. doi: 10.1099/0022-1317-45-3-737. [DOI] [PubMed] [Google Scholar]
- Price P., Winter J. G., Nikoletti S., Hudson J. B., Shellam G. R. Functional changes in murine macrophages infected with cytomegalovirus relate to H-2-determined sensitivity to infection. J Virol. 1987 Nov;61(11):3602–3606. doi: 10.1128/jvi.61.11.3602-3606.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Price P., Winter J. G., Shellam G. R. Genetically determined resistance to murine cytomegalovirus: a role for lymphocytostatic macrophages. J Gen Virol. 1987 Dec;68(Pt 12):2997–3008. doi: 10.1099/0022-1317-68-12-2997. [DOI] [PubMed] [Google Scholar]
- Quinnan G. V., Jr, Manischewitz J. F. Genetically determined resistance to lethal murine cytomegalovirus infection is mediated by interferon-dependent and -independent restriction of virus replication. J Virol. 1987 Jun;61(6):1875–1881. doi: 10.1128/jvi.61.6.1875-1881.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- RUSSELL W. C. A sensitive and precise plaque assay for herpes virus. Nature. 1962 Sep 8;195:1028–1029. doi: 10.1038/1951028a0. [DOI] [PubMed] [Google Scholar]
- Shellam G. R., Allan J. E., Papadimitriou J. M., Bancroft G. J. Increased susceptibility to cytomegalovirus infection in beige mutant mice. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5104–5108. doi: 10.1073/pnas.78.8.5104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shellam G. R., Flexman J. P., Farrell H. E., Papadimitriou J. M. The genetic background modulates the effect of the beige gene on susceptibility to cytomegalovirus infection in mice. Scand J Immunol. 1985 Aug;22(2):147–155. doi: 10.1111/j.1365-3083.1985.tb01867.x. [DOI] [PubMed] [Google Scholar]
- Shellam G. R., Flexman J. P. Genetically determined resistance to murine cytomegalovirus and herpes simplex virus in newborn mice. J Virol. 1986 Apr;58(1):152–156. doi: 10.1128/jvi.58.1.152-156.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simmons A., La Vista A. B. Neural infection in mice after cutaneous inoculation with HSV-1 is under complex host genetic control. Virus Res. 1989 Jul;13(3):263–270. doi: 10.1016/0168-1702(89)90020-8. [DOI] [PubMed] [Google Scholar]
- Simmons A., Nash A. A. Zosteriform spread of herpes simplex virus as a model of recrudescence and its use to investigate the role of immune cells in prevention of recurrent disease. J Virol. 1984 Dec;52(3):816–821. doi: 10.1128/jvi.52.3.816-821.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winkler S. R., Booss J. Comparison of techniques for recovering murine cytomegalovirus from a macrophage-enriched subpopulation of mice. J Clin Microbiol. 1980 Dec;12(6):785–789. doi: 10.1128/jcm.12.6.785-789.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zawatzky R., Gresser I., DeMaeyer E., Kirchner H. The role of interferon in the resistance of C57BL/6 mice to various doses of herpes simplex virus type 1. J Infect Dis. 1982 Sep;146(3):405–410. doi: 10.1093/infdis/146.3.405. [DOI] [PubMed] [Google Scholar]