Skip to main content
NCBI home page
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2002 Dec 11;142(1):5–15. doi: 10.1016/0923-2516(91)90022-U

Increased susceptibility to mouse hepatitis virus type 3 (MHV3) infection induced by a hypercholesterolaemic diet with increased adsorption of MHV3 to primary hepatocyte cultures

J Braunwald 1, H Nonnenmacher 1, CA Pereira 1, A Kirn 1
PMCID: PMC7135346  PMID: 1711237

Abstract

The administration of a hypercholesterolaemic (HC) diet rendered genetically resistant A/J mice susceptible to mouse hepatitis 3 (MHV3) infection. The animals died cf acute hepatitis with high viral titres in the liver accompanied by many necrotic foci and high serum transaminase levels. Resistance to virus was re-established by refeeding HC mice with a normal diet for 2 weeks. This of modification by pathogenesis was accompanied by an increase in the susceptibility of hepatocyte cultures from HC mice to MHV3 and could be explained by an enhancement in virus adsorption. We hypothesize that the incorporation of cholesterol into the plasma membranes of hepatocytes of HC mice, thereby decreasing the membrane fluidity, may lead to an increase in the availability of virus receptors.

Keywords: MHV3, Cholesterol, Hepatocyte; Membrane, Hypercholesterolaemic diet, Mouse, Cell culture, Pathogenesis

References

  1. Arnheiter H. Primary monolayer culture of adult mouse hepatocytes. A model for the study of hepatotropic viruses. Arch. Virol. 1980;63:11–22. doi: 10.1007/BF01320757. [DOI] [PubMed] [Google Scholar]
  2. Arnheiter H., Baechi T., Haller O. Adult mouse hepatocytes in primary monolayer culture express genetic resistance to mouse hepatitis virus type 3. J. Immunol. 1982;129:1275–1281. [PubMed] [Google Scholar]
  3. Berry M.N., Friend D.S. High-yield preparation of isolated rat liver parenchymal cells. J. Cell. Biol. 1969;43:506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bonner W.M., Laskey R.A. A film detection method of tritum-labeled proteins and nucleic acids in polyacrylamide gels. Europ. J. Biochem. 1974;46:83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  5. Borochov H., Shinitzky M. Vol. 73. 1976. Vertical displacement of membrane proteins mediated by changes in microviscosity; pp. 4526–4530. (Proc. nat. Acad. Sci. (Wash.)). [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Borochov H., Abbott R.E., Schachter D., Shinitzky M. Modulation of erythrocyte membrane proteins by membrane cholesterol and lipid fluidity. Biochemistry. 1979;18:251–255. doi: 10.1021/bi00569a002. [DOI] [PubMed] [Google Scholar]
  7. Campbell A.E., Loria A.E., Madge G.E., Kaplan A.M. Dietary hepatic cholesterol elevatiion: effects on coxsackievirus B infection and inflammation. Infect. Immun. 1982;37:307–317. doi: 10.1128/iai.37.1.307-317.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Collins A.R., Knobler R.L., Powell H., Buchmeier M.J. Monoclonal antibodies to murine hepatitis virus (strain JHM) define the viral glycoprotein responsible for attachment and cell-cell fusion. Virology. 1982;119:358–371. doi: 10.1016/0042-6822(82)90095-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Daya M., Cervin M., Anderson R. Cholesterol enhances ouse hepatitis-virus-mediated cell fusion. Virology. 1988;163:276–283. doi: 10.1016/0042-6822(88)90267-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Demel R.A., De Kruff B. The function of sterols in membranes. Biochem. biophys. Acta (Amst.) 1976;457:109–132. doi: 10.1016/0304-4157(76)90008-3. [DOI] [PubMed] [Google Scholar]
  11. Deschenes J., Valet J.P., Marceau N. Hepatocytes from newborn and weanling rats in monolayer culture: isolation by perfusion, fibronectin-mediated adhesion, spreading, and functional activities. In Vitro. 1980;16:722–730. doi: 10.1007/BF02619202. [DOI] [PubMed] [Google Scholar]
  12. Frana M.F., Behnke J.N., Sturman L.S., Holmes K.V. Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: host-dependent differences in proteolytic cleavage and cell fusion. J. Virol. 1985;56:912–920. doi: 10.1128/jvi.56.3.912-920.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Guguen-Guillouzo C., Guillouzo A. Méthodes de préparation d'hépatocytes adultes et foetaux. In: Guillouzo A., Guguen-Guillouzo C., editors. Recherches en… Hépatocytes isolés et en culture. INSERM, John Libbey Eurotext; Montrouge, France: 1986. pp. 1–12. [Google Scholar]
  14. Kirn A., Gut J.P., Gendrault J.L. Interaction of viruses with sinusoidal cells. In: Popper H., Schaffner F., editors. vol. 7. Grune and Stratton; New York: 1982. pp. 377–392. (Progress in liver diseases). [PubMed] [Google Scholar]
  15. Klauning J.E., Goldblatt P.J., Hinton D.E., Lipsky M.M., Chacko J., Trump B.F. Mouse liver cell culture. — I. Hepatocyte isolation. In Vitro. 1981;17:913–925. doi: 10.1007/BF02618288. [DOI] [PubMed] [Google Scholar]
  16. Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (Lond.) 1970;227:680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  17. Lamontagne L.M., Dupuy J.M. Natural resistance of mice to mouse hepatitis virus type 3 infection is expressed in embryonic fibroblast cells. J. gen. Virol. 1984;65:1165–1171. doi: 10.1099/0022-1317-65-7-1165. [DOI] [PubMed] [Google Scholar]
  18. Le Prévost 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;114:221–225. [PubMed] [Google Scholar]
  19. Le Prévost C., Virelizier J.L., Dupuy J.M. Immunopathology of mouse hepatitis virus type 3 infection.—III. Clinical and virologic observation of a persistent viral infection. J. Immunol. 1975;115:640–643. [PubMed] [Google Scholar]
  20. Loria R.M., Kibrick S., Madge G.E. Infection of hypercholesterolemic mice with coxsackievirus B. J. infect. Dis. 1976;133:655–662. doi: 10.1093/infdis/133.6.655. [DOI] [PubMed] [Google Scholar]
  21. Martin J.P., Koehren F., Rannou J.J., Kirn A. Temperature=sensitive mutants of mouse hepatitis virus type3 (MHV3): isolation, biochemical and genetic characterization. Arch. Virol. 1988;100:147–160. doi: 10.1007/BF01487679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Martin J.P., Chen W., Obert G., Koehren F. Characterization of attenuated mutants of MHV3: importance of E2 protein in organ tropism and infection of isolated liver cells. In: Cavanagh D., Brown D., editors. Molecular biology and pathogenicity of coronaviruses. Plenum Press; New York: 1990. (in press) [DOI] [PubMed] [Google Scholar]
  23. Maslansky C.J., Williams G.M. Primary cultures and the levels of cytochrome P450 in hepatocytes from mouse, rat, hamster and rabbit liver. In Vitro. 1982;18:683–693. doi: 10.1007/BF02796423. [DOI] [PubMed] [Google Scholar]
  24. Pereira C.A., Steffan A.M., Kirn A. Interaction between mouse hepatitis viruses and primary cultures of Kupffer and endothelial liver cells from resistant and susceptible inbred mouse strains. J. gen. Virol. 1984;65:1617–1620. doi: 10.1099/0022-1317-65-9-1617. [DOI] [PubMed] [Google Scholar]
  25. Pereira C.A., Steffan A.M., Kirn A. Kupffer and endothelial liver cell damage renders A/J mice susceptible to mouse hepatitis virus type 3. Virus Res. 1984;1:557–563. doi: 10.1016/0168-1702(84)90013-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pereira C.A., Steffan A.M., Klein F., Rebel G., Kirn A. Kupffer cells (KC) from mice fed a hypercholesterolemic diet (HC) have lost their ability to be activated by endotoxin in vitro. In: Kirn A., Knook D.L., Wisse E., editors. vol. I. The Kupffer Cell Foundation; Rijswijk, The Netherlands: 1986. (Cells of the hepatic sinusoid). [Google Scholar]
  27. 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;174:253–265. doi: 10.1016/S0171-2985(87)80001-3. [DOI] [PubMed] [Google Scholar]
  28. Renton K.W., Deloria L.B., Mannering G.J. Effects of polyriboinosinic acid-polyribocytidylic acid and a mouse interferon preparation on cytochrome P 450-dependent monooxygenase systems in cultures of primary mouse hepatocytes. Mol. Pharmacol. 1978;14:672–681. [PubMed] [Google Scholar]
  29. Seglen P.O. Preparation of isolated rat liver cells. In: Prescott D.M., editor. vol. 13. Academic Press; New York, London: 1976. (Methods in cell biology). [DOI] [PubMed] [Google Scholar]
  30. Shinitzky M., Inbar M. Microviscosity parameters and protein mobility in biological membranes. Biochem. biophys. Acta (Amst.) 1976;433:133–149. doi: 10.1016/0005-2736(76)90183-8. [DOI] [PubMed] [Google Scholar]
  31. Steffan A.M., Kirn A. Multiplication of vacinia virus in the livers of mice after frog virus 3-induced damage to sinusoidal cells. J. Reticuloendoth. Soc. 1979;26:531–538. [PubMed] [Google Scholar]
  32. Steffan A.M., Pereira C.A., Kirn A. Role of sinusoidal cells in the course of the hepatitis induced by mouse hepatitis virus type 3 (MHV3) in mice. In: Kirn A., Knook D.L., Wisse E., editors. vol. I. The Kupffer Cell Foundation; Rijswijk, The Netherlands: 1986. pp. 377–378. (Cells of the hepatic sinusoid). [Google Scholar]
  33. Sturman L.S., Holmes K.V. The molecular biology of coronaviruses. Advanc. Virus Res. 1983;28:35–112. doi: 10.1016/S0065-3527(08)60721-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sturman L.S., Ricard C.S., Holmes K.V. Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: activation of cell-fusing activity of virus by trypsin and separation of two different 90 K cleavage fragments. J. Virol. 1985;56:904–911. doi: 10.1128/jvi.56.3.904-911.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Virelizier J.L. Role of macrophages and interferon in natural resistance to mouse hepatitis virus infection. Curr. Top. Microbiol. Immunol. 1980;92:53–64. doi: 10.1007/978-3-642-68069-4_4. [DOI] [PubMed] [Google Scholar]
  36. Virelizier J.L., Allison A.C. Correlation of persistent mouse hepatitis virus (MHV3) infection with its effect on mouse macrophage cultures. Arch. Virol. 1976;50:279–285. doi: 10.1007/BF01317953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wege H., Dorries R., Wege H. Hybridoma antibodies to the murine coronavirus JHM: characterization of epitopes on the peplomer protein (E2) J. gen. Virol. 1984;65:1931–1942. doi: 10.1099/0022-1317-65-11-1931. [DOI] [PubMed] [Google Scholar]

Articles from Research in Virology are provided here courtesy of Elsevier

RESOURCES