Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Oct;70(10):6673–6681. doi: 10.1128/jvi.70.10.6673-6681.1996

Transgenic mice expressing human measles virus (MV) receptor CD46 provide cells exhibiting different permissivities to MV infections.

B Horvat 1, P Rivailler 1, G Varior-Krishnan 1, A Cardoso 1, D Gerlier 1, C Rabourdin-Combe 1
PMCID: PMC190709  PMID: 8794303

Abstract

We have generated transgenic mice ubiquitously expressing the human receptor for measles virus (MV), CD46 (membrane cofactor protein). Various cell types were isolated from these transgenic mice and analyzed for their ability to support MV replication in vitro. Although MV could enter into all CD46-expressing cells, differential susceptibilities to MV infection were detected depending on the cell type. Cell cultures obtained from transgenic lungs and kidneys were found to be permissive of MV infection, since RNA specific for MV genes was detected and viral particles were released, although at a low level. Similarly to human lymphocytes, activated T and B lymphocytes isolated from transgenic mice could support MV replication; virus could enter, transcribe viral RNA, and produce new infectious particles. When expressing viral proteins, lymphocytes down-regulated CD46 from the surface. Interestingly, while activated T lymphocytes from nontransgenic mice did not support MV infection, activated nontransgenic murine B lymphocytes replicated MV as well as transgenic B lymphocytes, suggesting the use of an alternative virus receptor for entry. In contrast to the previous cell types, murine peritoneal and bone marrow-derived macrophages, regardless of whether they were activated, could not support MV replication. Furthermore, although MV entered into macrophages and virus-specific RNA transcription occurred, no virus protein or infectious virus particles could be detected. These results show the importance of the particular cell-type-specific host factors for MV replication in murine cells which may be responsible for the differential permissivity of MV infection.

Full Text

The Full Text of this article is available as a PDF (289.2 KB).

Selected References

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

  1. Barbanti-Brodano G., Oyanagi S., Katz M., Koprowski H. Presence of 2 different viral agents in brain cells of patients with subacute sclerosing panencephalitis. Proc Soc Exp Biol Med. 1970 May;134(1):230–236. doi: 10.3181/00379727-134-34765. [DOI] [PubMed] [Google Scholar]
  2. Beauverger P., Buckland R., Wild T. F. Measles virus antigens induce both type-specific and canine distemper virus cross-reactive cytotoxic T lymphocytes in mice: localization of a common Ld-restricted nucleoprotein epitope. J Gen Virol. 1993 Nov;74(Pt 11):2357–2363. doi: 10.1099/0022-1317-74-11-2357. [DOI] [PubMed] [Google Scholar]
  3. Beckford A. P., Kaschula R. O., Stephen C. Factors associated with fatal cases of measles. A retrospective autopsy study. S Afr Med J. 1985 Dec 7;68(12):858–863. [PubMed] [Google Scholar]
  4. Bohn W., Rutter G., Hohenberg H., Mannweiler K., Nobis P. Involvement of actin filaments in budding of measles virus: studies on cytoskeletons of infected cells. Virology. 1986 Feb;149(1):91–106. doi: 10.1016/0042-6822(86)90090-5. [DOI] [PubMed] [Google Scholar]
  5. Cervoni F., Fenichel P., Akhoundi C., Hsi B. L., Rossi B. Characterization of a cDNA clone coding for human testis membrane cofactor protein (MCP, CD46). Mol Reprod Dev. 1993 Jan;34(1):107–113. doi: 10.1002/mrd.1080340117. [DOI] [PubMed] [Google Scholar]
  6. Dunster L. M., Schneider-Schaulies J., Löffler S., Lankes W., Schwartz-Albiez R., Lottspeich F., ter Meulen V. Moesin: a cell membrane protein linked with susceptibility to measles virus infection. Virology. 1994 Jan;198(1):265–274. doi: 10.1006/viro.1994.1029. [DOI] [PubMed] [Google Scholar]
  7. Dörig R. E., Marcil A., Chopra A., Richardson C. D. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell. 1993 Oct 22;75(2):295–305. doi: 10.1016/0092-8674(93)80071-l. [DOI] [PubMed] [Google Scholar]
  8. Esolen L. M., Ward B. J., Moench T. R., Griffin D. E. Infection of monocytes during measles. J Infect Dis. 1993 Jul;168(1):47–52. doi: 10.1093/infdis/168.1.47. [DOI] [PubMed] [Google Scholar]
  9. Gautier C., Mehtali M., Lathe R. A ubiquitous mammalian expression vector, pHMG, based on a housekeeping gene promoter. Nucleic Acids Res. 1989 Oct 25;17(20):8389–8389. doi: 10.1093/nar/17.20.8389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gerlier D., Loveland B., Varior-Krishnan G., Thorley B., McKenzie I. F., Rabourdin-Combe C. Measles virus receptor properties are shared by several CD46 isoforms differing in extracellular regions and cytoplasmic tails. J Gen Virol. 1994 Sep;75(Pt 9):2163–2171. doi: 10.1099/0022-1317-75-9-2163. [DOI] [PubMed] [Google Scholar]
  11. Gerlier D., Trescol-Biémont M. C., Varior-Krishnan G., Naniche D., Fugier-Vivier I., Rabourdin-Combe C. Efficient major histocompatibility complex class II-restricted presentation of measles virus relies on hemagglutinin-mediated targeting to its cellular receptor human CD46 expressed by murine B cells. J Exp Med. 1994 Jan 1;179(1):353–358. doi: 10.1084/jem.179.1.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Giraudon P., Wild T. F. Correlation between epitopes on hemagglutinin of measles virus and biological activities: passive protection by monoclonal antibodies is related to their hemagglutination inhibiting activity. Virology. 1985 Jul 15;144(1):46–58. doi: 10.1016/0042-6822(85)90303-4. [DOI] [PubMed] [Google Scholar]
  13. Hyypiä T., Korkiamäki P., Vainionpä R. Replication of measles virus in human lymphocytes. J Exp Med. 1985 Jun 1;161(6):1261–1271. doi: 10.1084/jem.161.6.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnstone R. W., Loveland B. E., McKenzie I. F. Identification and quantification of complement regulator CD46 on normal human tissues. Immunology. 1993 Jul;79(3):341–347. [PMC free article] [PubMed] [Google Scholar]
  15. Johnstone R. W., Russell S. M., Loveland B. E., McKenzie I. F. Polymorphic expression of CD46 protein isoforms due to tissue-specific RNA splicing. Mol Immunol. 1993 Oct;30(14):1231–1241. doi: 10.1016/0161-5890(93)90038-d. [DOI] [PubMed] [Google Scholar]
  16. Koike S., Taya C., Kurata T., Abe S., Ise I., Yonekawa H., Nomoto A. Transgenic mice susceptible to poliovirus. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):951–955. doi: 10.1073/pnas.88.3.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Laird P. W., Zijderveld A., Linders K., Rudnicki M. A., Jaenisch R., Berns A. Simplified mammalian DNA isolation procedure. Nucleic Acids Res. 1991 Aug 11;19(15):4293–4293. doi: 10.1093/nar/19.15.4293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Liebert U. G., Finke D. Measles virus infections in rodents. Curr Top Microbiol Immunol. 1995;191:149–166. doi: 10.1007/978-3-642-78621-1_10. [DOI] [PubMed] [Google Scholar]
  19. Liszewski M. K., Post T. W., Atkinson J. P. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol. 1991;9:431–455. doi: 10.1146/annurev.iy.09.040191.002243. [DOI] [PubMed] [Google Scholar]
  20. MILLER D. L. FREQUENCY OF COMPLICATIONS OF MEASLES, 1963. REPORT ON A NATIONAL INQUIRY BY THE PUBLIC HEALTH LABORATORY SERVICE IN COLLABORATION WITH THE SOCIETY OF MEDICAL OFFICERS OF HEALTH. Br Med J. 1964 Jul 11;2(5401):75–78. doi: 10.1136/bmj.2.5401.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Maisner A., Schneider-Schaulies J., Liszewski M. K., Atkinson J. P., Herrler G. Binding of measles virus to membrane cofactor protein (CD46): importance of disulfide bonds and N-glycans for the receptor function. J Virol. 1994 Oct;68(10):6299–6304. doi: 10.1128/jvi.68.10.6299-6304.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Malvoisin E., Wild F. Contribution of measles virus fusion protein in protective immunity: anti-F monoclonal antibodies neutralize virus infectivity and protect mice against challenge. J Virol. 1990 Oct;64(10):5160–5162. doi: 10.1128/jvi.64.10.5160-5162.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Malvoisin E., Wild F. The role of N-glycosylation in cell fusion induced by a vaccinia recombinant virus expressing both measles virus glycoproteins. Virology. 1994 Apr;200(1):11–20. doi: 10.1006/viro.1994.1157. [DOI] [PubMed] [Google Scholar]
  24. Manchester M., Liszewski M. K., Atkinson J. P., Oldstone M. B. Multiple isoforms of CD46 (membrane cofactor protein) serve as receptors for measles virus. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2161–2165. doi: 10.1073/pnas.91.6.2161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Matumoto M. Multiplication of measles virus in cell cultures. Bacteriol Rev. 1966 Mar;30(1):152–176. doi: 10.1128/br.30.1.152-176.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Moench T. R., Griffin D. E., Obriecht C. R., Vaisberg A. J., Johnson R. T. Acute measles in patients with and without neurological involvement: distribution of measles virus antigen and RNA. J Infect Dis. 1988 Aug;158(2):433–442. doi: 10.1093/infdis/158.2.433. [DOI] [PubMed] [Google Scholar]
  27. Mougneau E., Altare F., Wakil A. E., Zheng S., Coppola T., Wang Z. E., Waldmann R., Locksley R. M., Glaichenhaus N. Expression cloning of a protective Leishmania antigen. Science. 1995 Apr 28;268(5210):563–566. doi: 10.1126/science.7725103. [DOI] [PubMed] [Google Scholar]
  28. Moyer S. A., Baker S. C., Horikami S. M. Host cell proteins required for measles virus reproduction. J Gen Virol. 1990 Apr;71(Pt 4):775–783. doi: 10.1099/0022-1317-71-4-775. [DOI] [PubMed] [Google Scholar]
  29. Nakayama T., Mori T., Yamaguchi S., Sonoda S., Asamura S., Yamashita R., Takeuchi Y., Urano T. Detection of measles virus genome directly from clinical samples by reverse transcriptase-polymerase chain reaction and genetic variability. Virus Res. 1995 Jan;35(1):1–16. doi: 10.1016/0168-1702(94)00074-m. [DOI] [PubMed] [Google Scholar]
  30. Naniche D., Varior-Krishnan G., Cervoni F., Wild T. F., Rossi B., Rabourdin-Combe C., Gerlier D. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol. 1993 Oct;67(10):6025–6032. doi: 10.1128/jvi.67.10.6025-6032.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Naniche D., Wild T. F., Rabourdin-Combe C., Gerlier D. A monoclonal antibody recognizes a human cell surface glycoprotein involved in measles virus binding. J Gen Virol. 1992 Oct;73(Pt 10):2617–2624. doi: 10.1099/0022-1317-73-10-2617. [DOI] [PubMed] [Google Scholar]
  32. Naniche D., Wild T. F., Rabourdin-Combe C., Gerlier D. Measles virus haemagglutinin induces down-regulation of gp57/67, a molecule involved in virus binding. J Gen Virol. 1993 Jun;74(Pt 6):1073–1079. doi: 10.1099/0022-1317-74-6-1073. [DOI] [PubMed] [Google Scholar]
  33. Ogura H., Rima B. K., Tas P., Baczko K., ter Meulen V. Restricted synthesis of the fusion protein of measles virus at elevated temperatures. J Gen Virol. 1988 Apr;69(Pt 4):925–929. doi: 10.1099/0022-1317-69-4-925. [DOI] [PubMed] [Google Scholar]
  34. Poste G., Alexander D. J., Reeve P., Hewlett G. Modification of Newcastle disease virus release and cytopathogenicity in cells treated with plant lectins. J Gen Virol. 1974 Jun;23(3):255–270. doi: 10.1099/0022-1317-23-3-255. [DOI] [PubMed] [Google Scholar]
  35. Reeve P., Hewlett G., Watkins H., Alexander D. J., Poste G. Virus-induced cell fusion enhanced by phytohaemagglutinin. Nature. 1974 May 24;249(455):355–356. doi: 10.1038/249355a0. [DOI] [PubMed] [Google Scholar]
  36. Ren R. B., Costantini F., Gorgacz E. J., Lee J. J., Racaniello V. R. Transgenic mice expressing a human poliovirus receptor: a new model for poliomyelitis. Cell. 1990 Oct 19;63(2):353–362. doi: 10.1016/0092-8674(90)90168-e. [DOI] [PubMed] [Google Scholar]
  37. Salonen R., Ilonen J., Salmi A. Measles virus infection of unstimulated blood mononuclear cells in vitro: antigen expression and virus production preferentially in monocytes. Clin Exp Immunol. 1988 Feb;71(2):224–228. [PMC free article] [PubMed] [Google Scholar]
  38. Schneider-Schaulies J., Dunster L. M., Schwartz-Albiez R., Krohne G., ter Meulen V. Physical association of moesin and CD46 as a receptor complex for measles virus. J Virol. 1995 Apr;69(4):2248–2256. doi: 10.1128/jvi.69.4.2248-2256.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schneider-Schaulies S., Schneider-Schaulies J., Bayer M., Löffler S., ter Meulen V. Spontaneous and differentiation-dependent regulation of measles virus gene expression in human glial cells. J Virol. 1993 Jun;67(6):3375–3383. doi: 10.1128/jvi.67.6.3375-3383.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schulz T. F., Hoad J. G., Whitby D., Tizard E. J., Dillon M. J., Weiss R. A. A measles virus isolate from a child with Kawasaki disease: sequence comparison with contemporaneous isolates from 'classical' cases. J Gen Virol. 1992 Jun;73(Pt 6):1581–1586. doi: 10.1099/0022-1317-73-6-1581. [DOI] [PubMed] [Google Scholar]
  41. Stallcup K. C., Raine C. S., Fields B. N. Cytochalasin B inhibits the maturation of measles virus. Virology. 1983 Jan 15;124(1):59–74. doi: 10.1016/0042-6822(83)90290-8. [DOI] [PubMed] [Google Scholar]
  42. Vydelingum S., Suryanarayana K., Marusyk R. G., Salmi A. A. Replication of measles virus in human monocytes and T cells. Can J Microbiol. 1995 Jul;41(7):620–623. doi: 10.1139/m95-082. [DOI] [PubMed] [Google Scholar]
  43. Weiss R. Measles battle loses potent weapon. Science. 1992 Oct 23;258(5082):546–547. doi: 10.1126/science.1329205. [DOI] [PubMed] [Google Scholar]
  44. Wild T. F., Buckland R. Functional aspects of envelope-associated measles virus proteins. Curr Top Microbiol Immunol. 1995;191:51–64. doi: 10.1007/978-3-642-78621-1_4. [DOI] [PubMed] [Google Scholar]
  45. Yanagi Y., Hu H. L., Seya T., Yoshikura H. Measles virus infects mouse fibroblast cell lines, but its multiplication is severely restricted in the absence of CD46. Arch Virol. 1994;138(1-2):39–53. doi: 10.1007/BF01310037. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES