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. 1969 Feb 28;129(3):483–505. doi: 10.1084/jem.129.3.483

PATHOGENESIS OF CHRONIC DISEASE ASSOCIATED WITH PERSISTENT LYMPHOCYTIC CHORIOMENINGITIS VIRAL INFECTION

I. RELATIONSHIP OF ANTIBODY PRODUCTION TO DISEASE IN NEONATALLY INFECTED MICE

Michael B A Oldstone 1, Frank J Dixon 1
PMCID: PMC2138618  PMID: 4179834

Abstract

Mice infected shortly after birth with lymphocytic choriomeningitis (LCM) virus are not immunologically tolerant, although they carry the virus throughout life. These LCM carrier mice make anti-LCM antibody, which apparently complexes with viral antigen in the circulation and these complexes accumulate in the glomeruli. LCM carrier mice of different strains vary significantly as to concentration of detectable infectious virus in their tissue, amount and time of appearance of anti-LCM antibody, and development of an associated chronic disease. The chronic disease consists primarily of glomerulonephritis, focal hepatic necrosis, and disseminated lymphoid infiltrations. LCM carriers of the SWR/J strain contain high tissue concentrations of virus, considerable anti-LCM antibody detectable in the glomeruli by 3 wk to 2 months of age and develop chronic disease within the first 2–3 months of life. In contrast, C3H strain LCM carriers contain 1/1000 as much infectious virus, less detectable anti-LCM antibody, and have not, over a 24 month observation period, developed any detectable disease. B10D2 old and new carrier mice with intermediate amounts of virus develop chronic disease during the latter half of the first year of life. The pathogenesis of the glomerulonephritis of chronic LCM disease is apparently related to the formation of circulating virus-antibody complexes which are trapped in the glomerular filter. There is no evidence for direct glomerular injury by the virus nor for any autoimmune response by the host.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker F. D., Hotchin J. Slow virus kidney disease of mice. Science. 1967 Oct 27;158(3800):502–504. doi: 10.1126/science.158.3800.502. [DOI] [PubMed] [Google Scholar]
  2. DIXON F. J., FELDMAN J. D., VAZQUEZ J. J. Experimental glomerulonephritis. The pathogenesis of a laboratory model resembling the spectrum of human glomerulonephritis. J Exp Med. 1961 May 1;113:899–920. doi: 10.1084/jem.113.5.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. FAHEY J. L., MCKELVEY E. M. QUANTITATIVE DETERMINATION OF SERUM IMMUNOGLOBULINS IN ANTIBODY-AGAR PLATES. J Immunol. 1965 Jan;94:84–90. [PubMed] [Google Scholar]
  4. FENNELL R. H., Jr, SANTAMARIA A. Anaphylaxis in the rat. Immunohistochemical and histochemical studies of the liver. Am J Pathol. 1962 Nov;41:521–534. [PMC free article] [PubMed] [Google Scholar]
  5. FERNANDES M. V., WIKTOR T. J., KOPROWSKI H. ENDOSYMBIOTIC RELATIONSHIP BETWEEN ANIMAL VIRUSES AND HOST CELLS. A STUDY OF RABIES VIRUS IN TISSUE CULTURE. J Exp Med. 1964 Dec 1;120:1099–1116. doi: 10.1084/jem.120.6.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. HAAS V. H., STEWART S. E. Sparing effect of A-methopterin and guanazolo in mice infected with virus of lymphocytic choriomeningitis. Virology. 1956 Aug;2(4):511–516. doi: 10.1016/0042-6822(56)90007-1. [DOI] [PubMed] [Google Scholar]
  7. HOTCHIN J. E., CINITS M. Lymphocytic choriomeningitis infection of mice as a model for the study of latent virus infection. Can J Microbiol. 1958 Apr;4(2):149–163. doi: 10.1139/m58-016. [DOI] [PubMed] [Google Scholar]
  8. HOTCHIN J., COLLINS D. N. GLOMERULONEPHRITIS AND LATE ONSET DISEASE OF MICE FOLLOWING NEONATAL VIRUS INFECTION. Nature. 1964 Sep 26;203:1357–1359. doi: 10.1038/2031357a0. [DOI] [PubMed] [Google Scholar]
  9. HOTCHIN J. The biology of lymphocytic choriomeningitis infection: virus-induced immune disease. Cold Spring Harb Symp Quant Biol. 1962;27:479–499. doi: 10.1101/sqb.1962.027.001.046. [DOI] [PubMed] [Google Scholar]
  10. HOTCHIN J., WEIGAND H. The effects of pretreatment with x-rays on the pathogenesis of lymphocytic choriomeningitis in mice. I. Host survival, virus multiplication and leukocytosis. J Immunol. 1961 Dec;87:675–681. [PubMed] [Google Scholar]
  11. Hirsch M. S., Murphy F. A., Hicklin M. D. Immunopathology of lymphocytic choriomeningitis viurs infection of newborn mice. Antithymocyte serum effects on glomerulonephritis and wasting disease. J Exp Med. 1968 Apr 1;127(4):757–766. doi: 10.1084/jem.127.4.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hirsch M. S., Murphy F. A., Russe H. P., Hicklin M. D. Effects of anti-thymocyte serum on lymphocytic choriomeningitis (LCM) virus infection in mice. Proc Soc Exp Biol Med. 1967 Jul;125(3):980–983. doi: 10.3181/00379727-125-32254. [DOI] [PubMed] [Google Scholar]
  13. LINSCOTT W. D., COCHRANE C. G. GUINEA PIG BETA-1C-GLOBULIN: ITS RELATIONSHIP TO THE THIRD COMPONENT OF COMPLEMENT AND ITS ALTERATION FOLLOWING INTERACTION WITH IMMUNE COMPLEXES. J Immunol. 1964 Dec;93:972–984. [PubMed] [Google Scholar]
  14. Lambert P. H., Dixon F. J. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968 Mar 1;127(3):507–522. doi: 10.1084/jem.127.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  16. McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
  17. Mims C. A. Immunofluorescence study of the carrier state and mechanism of vertical transmission in lymphocytic choriomeningitis virus infection in mice. J Pathol Bacteriol. 1966 Apr;91(2):395–402. doi: 10.1002/path.1700910214. [DOI] [PubMed] [Google Scholar]
  18. Oldstone M. B., Dixon F. J. Direct immunofluorescent tissue culture assay for lymphocytic choriomeningitis virus. J Immunol. 1968 May;100(5):1135–1138. [PubMed] [Google Scholar]
  19. Oldstone M. B., Dixon F. J. Immunohistochemical study of allergic encephalomyelitis. Am J Pathol. 1968 Feb;52(2):251–263. [PMC free article] [PubMed] [Google Scholar]
  20. Oldstone M. B., Dixon F. J. Lymphocytic choriomeningitis: production of antibody by "tolerant" infected mice. Science. 1967 Dec 1;158(3805):1193–1195. doi: 10.1126/science.158.3805.1193. [DOI] [PubMed] [Google Scholar]
  21. Oldstone M. B., Dixon F. J. Susceptibility of different mouse strains to lymphocytic choriomeningitis virus. J Immunol. 1968 Feb;100(2):355–357. [PubMed] [Google Scholar]
  22. ROWE W. P. Protective effect of pre-irradiation on lymphocytic choriomeningitis infection in mice. Proc Soc Exp Biol Med. 1956 May;92(1):194–198. doi: 10.3181/00379727-92-22425. [DOI] [PubMed] [Google Scholar]
  23. Traub E. A FILTERABLE VIRUS RECOVERED FROM WHITE MICE. Science. 1935 Mar 22;81(2099):298–299. doi: 10.1126/science.81.2099.298. [DOI] [PubMed] [Google Scholar]
  24. Traub E. EPIDEMIOLOGY OF LYMPHOCYTIC CHORIOMENINGITIS IN A MOUSE STOCK OBSERVED FOR FOUR YEARS. J Exp Med. 1939 May 31;69(6):801–817. doi: 10.1084/jem.69.6.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Traub E. FACTORS INFLUENCING THE PERSISTENCE OF CHORIOMENINGITIS VIRUS IN THE BLOOD OF MICE AFTER CLINICAL RECOVERY. J Exp Med. 1938 Jul 31;68(2):229–250. doi: 10.1084/jem.68.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Traub E. PERSISTENCE OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS IN IMMUNE ANIMALS AND ITS RELATION TO IMMUNITY. J Exp Med. 1936 May 31;63(6):847–861. doi: 10.1084/jem.63.6.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. UNANUE E., DIXON F. J. EXPERIMENTAL GLOMERULONEPHRITIS. IV. PARTICIPATION OF COMPLEMENT IN NEPHROTOXIC NEPHRITIS. J Exp Med. 1964 Jan 1;119:965–982. doi: 10.1084/jem.119.6.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Unanue E. R., Dixon F. J. Experimental glomerulonephritis: immunological events and pathogenetic mechanisms. Adv Immunol. 1967;6:1–90. doi: 10.1016/s0065-2776(08)60521-0. [DOI] [PubMed] [Google Scholar]
  29. VOLKERT M., LARSEN J. H. STUDIES ON IMMUNOLOGICAL TOLERANCE TO LCM VIRUS. 3. DURATION AND MAXIMAL EFFECT OF ADOPTIVE IMMUNIZATION OF VIRUS CARRIERS. Acta Pathol Microbiol Scand. 1964;60:577–587. doi: 10.1111/apm.1964.60.4.577. [DOI] [PubMed] [Google Scholar]
  30. WASSERMAN E., LEVINE L. Quantitative micro-complement fixation and its use in the study of antigenic structure by specific antigen-antibody inhibition. J Immunol. 1961 Sep;87:290–295. [PubMed] [Google Scholar]

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