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. 1992;125(1):39–52. doi: 10.1007/BF01309627

Responses of mice to murine coronavirus immunization

A L Smith 1,2, M S de Souza 1,2, D Finzi 2, S W Barthold 1
PMCID: PMC7087131  PMID: 1322658

Summary

Oral and/or intranasal inoculation of susceptible mouse genotypes with the JHM strain of mouse hepatitis virus (MHV-JHM) consistently results in T cell dysfunction as reflected by in vitro proliferative responses to mitogens or allogeneic cells. One approach to examining the mechanism responsible for the observed functional T cell suppression is to determine whether virus replication is required for its induction. To this end, mice were inoculated oronasally with MHV-JHM that was inactivated with short-wave ultraviolet light, betapropiolactone or psoralen. Mice were also inoculated with live MHV-JHM after recovery from homotypic or heterotypic MHV infection. Spleen cells from BALB mice inoculated oronasally with inactivated MHV-JHM yielded extremely variable in vitro proliferative responses after concanavalin A stimulation. MHV-susceptible mice exposed oronasally or intraperitoneally to virus inactivated by any of the minimum effective treatments failed to seroconvert. Immunization with psoralen-treated virus intraperitoneally in Freund's complete adjuvant or oronasally failed to protect from live virus challenge, but survivors had elevated virus-specific serum IgG antibody titers compared to mock-immunized controls at two weeks post-challenge. Spleen cells from mice that were challenged after recovery from homotypic live virus infection did not exhibit the profound in vitro T cell suppression normally observed during the acute stage of primary infection. In contrast, MHV-JHM challenge of mice vaccinated with heterotypic live MHV-S resulted in significantly depressed in vitro T cell function. The combined data suggest that either virus replication or exposure to more concentrated antigen may be required for induction of the dramatic T cell dysfunction that occurs as a consequence of MHV-JHM infection as well as for a detectable MHV-specific humoral response.

Keywords: Spleen Cell, Psoralen, Live Virus, Mouse Hepatitis Virus, Intranasal Inoculation

References

  • 1.Barthold SW, Smith AL. Response of genetically susceptible and resistant mice to intranasal inoculation with mouse heptatitis virus JHM. Virus Res. 1987;7:225–239. doi: 10.1016/0168-1702(87)90030-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Barthold SW, Smith AL. Virus strain specificity of challenge immunity to coronavirus. Arch Virol. 1989;104:187–196. doi: 10.1007/BF01315542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Bia FJ, Thornton GF, Main AJ, Fong CKY, Hsiung GD. Western equine encephalitis mimicking herpes simplex encephalitis. J Am Med Assoc. 1980;244:367–369. [PubMed] [Google Scholar]
  • 4.Boorman GA, Luster MI, Dean JH, Campbell ML, Lauer LA, Talley FA, Wilson RE, Collins MJ. Peritoneal macrophage alterations caused by naturally occurring mouse hepatitis virus. Am J Pathol. 1982;106:110–117. [PMC free article] [PubMed] [Google Scholar]
  • 5.Braunsteiner H, Friend C. Viral hepatitis associated with transplantable mouse leukemia. J Exp Med. 1954;100:665–677. doi: 10.1084/jem.100.6.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Brownstein DG, Barthold SW. Mouse hepatitis virus immunofluorescence in formalin- or Bouin's-fixed tissues using trypsin digestion. Lab Anim Sci. 1982;32:37–39. [PubMed] [Google Scholar]
  • 7.Buckley SM, Casals J. Lassa fever, a new virus disease of man from West Africa. III. Isolation and characterization of the viurs. Am J Trop Med Hyg. 1970;19:680–691. doi: 10.4269/ajtmh.1970.19.680. [DOI] [PubMed] [Google Scholar]
  • 8.Carter JJ, Weinberg AD, Pollard A, Reeves R, Magnuson JA, Magnuson NS. Inhibition of T-lymphocyte mitogenic responses and effects on cell functions by bovine herpesvirus 1. J Virol. 1989;63:1525–1530. doi: 10.1128/jvi.63.4.1525-1530.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Casebolt DB, Spalding DM, Schoeb TR, Lindsey JR. Suppression of immune response induction in Peyer's patch lymphoid cells from mice infected with mouse hepatitis virus. Cell Immunol. 1987;109:97–103. doi: 10.1016/0008-8749(87)90295-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Cimino GD, Gamper HB, Isaacs ST, Hearst JE. Psoralens as photoactive probes of nucleic acid structure and function: organic chemistry, photochemistry, and biochemistry. Annu Rev Biochem. 1985;54:1151–1193. doi: 10.1146/annurev.bi.54.070185.005443. [DOI] [PubMed] [Google Scholar]
  • 11.Colonna Romano G, Dieli F, Abrignani S, Salerno A, Colizzi V. Inhibition of lymphocyte mitogenesis in mice infected with Newcastle disease virus: viral interference with the interleukin system. Immunology. 1986;57:373–378. [PMC free article] [PubMed] [Google Scholar]
  • 12.Dempsey WL, Smith AL, Morahan PS. Effect of inapparent murine hepatitis virus infections on macrophages and host resistance. J Leuk Biol. 1986;39:559–565. doi: 10.1002/jlb.39.5.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.de Souza MS, Smith AL. Characterization of accessory cell function during acute infection of BALB/cByJ mice with mouse hepatitis virus (MHV), strain JHM. Lab Anim Sci. 1991;41:112–118. [PubMed] [Google Scholar]
  • 14.de Souza MS, Smith AL, Bottomly K. Infection of BALB/cByJ mice with the JHM strain of mouse hepatitis virus alters in vitro splenic T cell proliferation and cytokine production. Lab Anim Sci. 1991;41:99–105. [PubMed] [Google Scholar]
  • 15.Engers HD, Louis JA, Zubler RH, Hirt B. Inhibition of T cell-mediated functions by MVM(i), a parvovirus closely related to minute virus of mice. J Immunol. 1981;127:2280–2285. [PubMed] [Google Scholar]
  • 16.Gillis S, Ferm MM, Ou W, Smith KA. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978;120:2027–2032. [PubMed] [Google Scholar]
  • 17.Hanson CV. Inactivation of viruses for use as vaccines and immunodiagnostic reagents. In: de la Maza LM, Peterson EM, editors. Medical virology II. New York: Elsevier; 1983. pp. 45–79. [Google Scholar]
  • 18.Harty JT, Plagemann PG. Formalin inactivation of the lactate dehydrogenase-elevating virus reveals a major neutralizing epitope not recognized during natural infection. J Virol. 1988;62:3210–3216. doi: 10.1128/jvi.62.9.3210-3216.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Homberger FR, Smith AL, Barthold SW. Detection of rodent coronaviruses in tissues and cell cultures using polymerase chain reaction. J Clin Microbiol. 1991;29:2789–2793. doi: 10.1128/jcm.29.12.2789-2793.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Hu-Li J, Ohara J, Watson C, Tsang W, Paul WE. Derivation of a T cell line that is highly responsive to IL-4 and IL-2 (CT.4R) and of an IL-2 hyporesponsive mutant of that line (CT.4S) J Immunol. 1989;142:800–807. [PubMed] [Google Scholar]
  • 21.Kraft V, Meyer B. Diagnosis of murine infections in relation to test methods employed. Lab Anim Sci. 1986;36:271–276. [PubMed] [Google Scholar]
  • 22.Lindsey JR. Prevalence of viral and mycoplasmal infections in laboratory rodents. In: Bhatt PN, Jacoby RO, Morse HC, New A, editors. Viral and mycoplasmal infections of laboratory rodents. Effects on biomedical research. New York: Academic Press; 1986. pp. 801–808. [Google Scholar]
  • 23.LoGrippo GA, Hartman FW. Antigenicity of beta-propiolactone-inactivated virus vaccines. J Immunol. 1955;75:123–128. [PubMed] [Google Scholar]
  • 24.Lucas CJ, Ubels-Postma JC, Rezee A, Galama JMD. Activation of measles virus from silently infected human lymphocytes. J Exp Med. 1978;148:940–952. doi: 10.1084/jem.148.4.940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Lussier G, Descoteaux J-P. Prevalence of natural virus infection in laboratory mice and rats used in Canada. Lab Anim Sci. 1986;36:145–148. [PubMed] [Google Scholar]
  • 26.McChesney MB, Altmann A, Oldstone MBA. Suppression of T lymphocyte function by measles virus is due to cell cycle arrest in G1. J Immunol. 1988;140:1269–1273. [PubMed] [Google Scholar]
  • 27.Margolese RG, Israel E, Wainberg MA. Non-specific inhibition by virus particles of human lymphocyte mitogenesis. Clin Exp Immunol. 1980;41:243–251. [PMC free article] [PubMed] [Google Scholar]
  • 28.Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine T helper cell clones. I. Definition according to profile of lymphokine activities. J Immunol. 1986;136:2348–2357. [PubMed] [Google Scholar]
  • 29.Ohara J, Paul WE. B cell stimulatory factor BSF-1: production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985;315:333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
  • 30.Small JD, New AE. Prevention and control of mousepox. Lab Anim Sci. 1981;31:616–621. [PubMed] [Google Scholar]
  • 31.Smith AL. An immunofluorescence test for detection of serum antibody to rodent coronaviruses. Lab Anim Sci. 1983;33:157–160. [PubMed] [Google Scholar]
  • 32.Smith AL, Barthold SW, de Souza MS, Bottomly K. The role of gamma interferon in infection of susceptible mice with murine coronavirus, MHV-JHM. Arch Virol. 1991;121:89–100. doi: 10.1007/BF01316746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Smith AL, Bottomly K, Winograd DF. Altered splenic T cell function of BALB/cByJ mice infected with mouse hepatitis virus or Sendai virus. J Immunol. 1987;138:3426–3430. [PubMed] [Google Scholar]
  • 34.Smith AL, Casals J, Main AJ. Antigenic characterization of Tettnang virus: Complications caused by passage of the virus in mice from a colony enzootically infected with mouse hepatitis virus. Am J Trop Med Hyg. 1983;32:1172–1176. doi: 10.4269/ajtmh.1983.32.1172. [DOI] [PubMed] [Google Scholar]
  • 35.Smith AL, Winograd DF. Two enzyme immunoassays for the detection of antibody to rodent coronaviruses. J Virol Methods. 1986;14:335–343. doi: 10.1016/0166-0934(86)90035-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Smith AL, Winograd DF, de Souza MS. In vitro splenic T cell responses of diverse mouse genotypes after oronasal exposure to mouse hepatitis virus, strain JHM. Lab Anim Sci. 1991;41:106–111. [PubMed] [Google Scholar]
  • 37.Strayer DS, Skaletsky E, Leibowitz JL. Inhibition of virus replication does not alter malignant rabbit fibroma virus-induced immunosuppression. Clin Exp Immunol. 1986;66:25–36. [PMC free article] [PubMed] [Google Scholar]
  • 38.Suzuki E, Matsubara J, Saito M, Muto T, Nakagawa M, Imaizumi K. Serological survey of laboratory rodents for infection with Sendai virus, mouse hepatitis virus, reovirus type 3 and mouse adenovirus. Jpn J Med Sci Biol. 1982;35:249–254. doi: 10.7883/yoken1952.35.249. [DOI] [PubMed] [Google Scholar]
  • 39.Wainberg MA, Israel E. Viral inhibition of lymhocyte mitogenesis. I. Evidence for nonspecificity of the effect. J Immunol. 1980;124:64–70. [PubMed] [Google Scholar]
  • 40.Wainberg MA, Portnoy JD, Clecner B, Hubschman S, Lagace-Simard J, Rabinovitch N, Remer Z, Mendelson J. Viral inhibition of lymphocyte proliferative responsiveness in patients suffering from recurrent lesions caused by herpes simplex virus. J Infect Dis. 1985;152:441–448. doi: 10.1093/infdis/152.3.441. [DOI] [PubMed] [Google Scholar]
  • 41.Watson J, Gillis S, Marbrook J, Mochizuki D, Smith KA. Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines. J Exp Med. 1979;150:849–861. doi: 10.1084/jem.150.4.849. [DOI] [PMC free article] [PubMed] [Google Scholar]

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