Abstract
Resistance of mice to mouse hepatitis virus type 3 (MHV3) infection is genetically determined. Normal adult A/J mice are resistant, and BALB/c mice are susceptible. Higher titers of virus and interferon (IFN) in vivo were found in MHV3-infected BALB/c mice compared with A/J mice. In vitro activation of macrophages (MФ) by lipopolysaccharide (LPS) delayed MHV3 replication only in cells that originated from A/J mice, although cell populations from both A/J, and BALB/c mice were able to synthesize comparable amounts of IFN-α/β. Using specific antibodies, we have shown that the delayed MHV3 replication in LPS-activated A/J MФ was due, in part, to IFN-α/β. A/J MФ were found to be more sensitive to IFN-γ than to IFN-α/β, and BALB/c MФ did not develop an antiviral state to either IFN. Cultured spleen cells from A/J mice synthesized more IFN-γ than BALB/c spleen cells after specific or non-specific stimulation. The results indicate that IFN-activated MФ may play a crucial role in the resistance to MHV3 infection. Since IFN-γ is produced in large amounts by A/J spleen cells after specific stimulation with MHV3 and is efficient in activating the A/J MФ, a T cell-dependent mechanism- is likely to be involved.
Footnotes
This work was supported in part by grants from the Fundacao de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Pesquisas (CNPq). M.A.L. was a recipient of the Deutscher Akademischer Austauschdienst (DAAD) during part of this research.
References
- 1.BANG F. B, WARWICK A. Mouse macrophages as host cells for the mouse hepatitis virus and the genetic basis of their susceptibility. Proc. Natl. Acad. Sci. USA. 1960;46:1065. doi: 10.1073/pnas.46.8.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.VIRELIZIER L. Role of macrophages and interferon in natural resistance to mouse hepatitis virus infections. Curr. Top. Microbiol. Immunol. 1960;92:53. doi: 10.1007/978-3-642-68069-4_4. [DOI] [PubMed] [Google Scholar]
- 3.LE PREVOST C., LEVY-LEBLOND E., VIRELIZIER J.L., DUPUY J.M. Immunopathology of mouse hepatitis virus type 3 infection. I. Role of humoral and cell mediated immunity in resistance mechanisms. J. Immunol. 1975;114:221. [PubMed] [Google Scholar]
- 4.PEREIRA C.A., STEFFAN A.M., KIRN A. Interactions between mouse hepatitis viruses and primary cultures of Kupffer and endothelial liver cells from resistant and susceptible inbred mouse strains. J. Gen. Virol. 1984;65:1617. doi: 10.1099/0022-1317-65-9-1617. [DOI] [PubMed] [Google Scholar]
- 5.LEVY G.A., LEIBOWITZ J.L., EDGINGTON T.S. Induction of monocyte procoagulant activity by murine hepatitis virus type 3 (MHV3) parallels disease susceptibility in mice. J. Exp. Med. 1981;154:1150. doi: 10.1084/jem.154.4.1150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.PEREIRA C.A., STEFFAN A.M., KOEHREN F., DOUGLAS C.R., KIRN A. Increased susceptibility of mice to MHV3 infection induced by hypercholesterolemic diet: Impairment of Kupffer cell function. Immunobiol. 1987;174:253. doi: 10.1016/S0171-2985(87)80001-3. [DOI] [PubMed] [Google Scholar]
- 7.SHIF I., BANG. F.B. In vitro interactions of mouse hepatitis virus and macrophages from genetically resistant mice. I. Adsorption of virus and growth curves. J. Exp. Med. 1970;1312:843. doi: 10.1084/jem.131.4.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.DUPUY J.M., LEVY-LEBLOND E., LE PREVOST C. Immunopathology of mouse hepatitis virus type 3 infection. II. Effect of immunosuppression in resistant mice. J. Immunol. 1975;114:226. [PubMed] [Google Scholar]
- 9.DUPUY J.M., DUPUY C., DECARIE D. Genetically determined resistance to mouse hepatitis virus type 3 is expressed in hematopoietic donor cells in radiation chimeras. J. Immunol. 1984;133:1609. [PubMed] [Google Scholar]
- 10.PEREIRA C.A., MERCIER G., OTH D., DUPUY J.M. Induction of natural killer cells and interferon during mouse hepatitis virus infection of resistant and susceptible inbred mouse strains. Immunobiol. 1984;166:35. doi: 10.1016/S0171-2985(84)80141-2. [DOI] [PubMed] [Google Scholar]
- 11.DIJKMANS R., HEREMANS H., BILLIAU A. Heterogeneity of Chinese hamster ovary cell produced recombinant murine Interferon gamma. J. Biol. Chem. 1987;262:2528. [PubMed] [Google Scholar]
- 12.PEREIRA C.A., STEFFAN A.M., KOEHREN F., KIRN A. Inhibition of mouse hepatitis virus type 3 multiplication in activated Kupffer cells. Braz. J. Med. Biol. Res. 1985;18:527. [PubMed] [Google Scholar]
- 13.TER MEULEN V. In: Coronavirus. LAI M.M. C., STOHLMAN S.A., editors. Plenum Press; New York: 1987. Biology of Coronavirus; p. 277. [Google Scholar]
- 14.TAGUCHI F., GOTO Y., AIUCHI M., HAYASHI T., FUJIWARA K. Pathogenesis of mouse hepatitis virus infection. The role of nasal epithelial cells as a primary target of lowvirulence virus, MHV-S. Microbiol. Immunol. 1979;23:249. doi: 10.1111/j.1348-0421.1979.tb00461.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.VIRELIZIER J.L., GRESSER I. Role of interferon in the pathogenesis of viral diseases of mice as demonstrated by the use of anti-interferon serum. V. Protective role in mouse hepatitis virus type 3 infection of susceptible and resistant strains of mice. J. Immunol. 1978;120:1616. [PubMed] [Google Scholar]
- 16.DINDZANS V.J., SKAMENE E., LEVY G.A. Susceptibility/resistance to mouse hepatitis virus strain 3 and macrophage procoagulant activity are linked and controlled by two non-H-2-linked genes. J. Immunol. 1986;137:2355. [PubMed] [Google Scholar]
- 17.SCHINDLER L., STREISSLE G., KIRCHNER H. Protection of mice against mouse hepatitis virus by Corynebacterium parvum. Infect. Immun. 1981;32:1128. doi: 10.1128/iai.32.3.1128-1131.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]