Abstract
Measles viruses (MV) can be isolated from the brains of deceased subacute sclerosing panencephalitis patients only in a cell-associated form. These viruses are often defective in the matrix (M) protein and always seem to have an altered fusion protein cytoplasmic tail. We reconstituted a cell-free, infectious M-less MV (MV-DeltaM) from cDNA. In comparison with standard MV, MV-DeltaM was considerably more efficient at inducing cell-to-cell fusion but virus titres were reduced approximately 250-fold. In MV-DeltaM-induced syncytia the ribonucleocapsids and glycoproteins largely lost co-localization, confirming the role of M protein as the virus assembly organizer. Genetically modified mice were inoculated with MV-DeltaM or with another highly fusogenic virus bearing glycoproteins with shortened cytoplasmic tails (MV-Delta(tails)). MV-DeltaM and MV-Delta(tails) lost acute pathogenicity but penetrated more deeply into the brain parenchyma than standard MV. We suggest that enhanced cell fusion may also favour the propagation of mutated, assembly-defective MV in human brains.
Full Text
The Full Text of this article is available as a PDF (901.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andersson T., Schwarcz R., Löve A., Kristensson K. Measles virus-induced hippocampal neurodegeneration in the mouse: a novel, subacute model for testing neuroprotective agents. Neurosci Lett. 1993 May 14;154(1-2):109–112. doi: 10.1016/0304-3940(93)90183-l. [DOI] [PubMed] [Google Scholar]
- Baczko K., Lampe J., Liebert U. G., Brinckmann U., ter Meulen V., Pardowitz I., Budka H., Cosby S. L., Isserte S., Rima B. K. Clonal expansion of hypermutated measles virus in a SSPE brain. Virology. 1993 Nov;197(1):188–195. doi: 10.1006/viro.1993.1579. [DOI] [PubMed] [Google Scholar]
- Bohn W., Rutter G., Hohenberg H., Mannweiler K. Inhibition of measles virus budding by phenothiazines. Virology. 1983 Oct 15;130(1):44–55. doi: 10.1016/0042-6822(83)90116-2. [DOI] [PubMed] [Google Scholar]
- Brody B. A., Rhee S. S., Sommerfelt M. A., Hunter E. A viral protease-mediated cleavage of the transmembrane glycoprotein of Mason-Pfizer monkey virus can be suppressed by mutations within the matrix protein. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3443–3447. doi: 10.1073/pnas.89.8.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buchholz C. J., Schneider U., Devaux P., Gerlier D., Cattaneo R. Cell entry by measles virus: long hybrid receptors uncouple binding from membrane fusion. J Virol. 1996 Jun;70(6):3716–3723. doi: 10.1128/jvi.70.6.3716-3723.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Büechi M., Bächi T. Microscopy of internal structures of Sendai virus associated with the cytoplasmic surface of host membranes. Virology. 1982 Jul 30;120(2):349–359. doi: 10.1016/0042-6822(82)90036-8. [DOI] [PubMed] [Google Scholar]
- Carrigan D. R. Round cell variant of measles virus: neurovirulence and pathogenesis of acute encephalitis in newborn hamsters. Virology. 1986 Jan 30;148(2):349–359. doi: 10.1016/0042-6822(86)90331-4. [DOI] [PubMed] [Google Scholar]
- Carrigan D. R. Round cell variant of measles virus: spontaneous conversion from productive to cell-associated state of infection. Virology. 1985 Jul 30;144(2):337–350. doi: 10.1016/0042-6822(85)90276-4. [DOI] [PubMed] [Google Scholar]
- Cathomen T., Naim H. Y., Cattaneo R. Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence. J Virol. 1998 Feb;72(2):1224–1234. doi: 10.1128/jvi.72.2.1224-1234.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cattaneo R., Rebmann G., Schmid A., Baczko K., ter Meulen V., Billeter M. A. Altered transcription of a defective measles virus genome derived from a diseased human brain. EMBO J. 1987 Mar;6(3):681–688. doi: 10.1002/j.1460-2075.1987.tb04808.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cattaneo R., Rose J. K. Cell fusion by the envelope glycoproteins of persistent measles viruses which caused lethal human brain disease. J Virol. 1993 Mar;67(3):1493–1502. doi: 10.1128/jvi.67.3.1493-1502.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cattaneo R., Schmid A., Eschle D., Baczko K., ter Meulen V., Billeter M. A. Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell. 1988 Oct 21;55(2):255–265. doi: 10.1016/0092-8674(88)90048-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Mareuil J., Salaun D., Chermann J. C., Hirsch I. Fusogenic determinants of highly cytopathic subtype D Zairian isolate HIV-1 NDK. Virology. 1995 Jun 1;209(2):649–653. doi: 10.1006/viro.1995.1298. [DOI] [PubMed] [Google Scholar]
- Eastman C. L., Urbańska E., Löve A., Kristensson K., Schwarcz R. Increased brain quinolinic acid production in mice infected with a hamster neurotropic measles virus. Exp Neurol. 1994 Jan;125(1):119–124. doi: 10.1006/exnr.1994.1015. [DOI] [PubMed] [Google Scholar]
- Fujinami R. S., Sissons J. G., Oldstone M. B. Immune reactive measles virus polypeptides on the cell's surface: turnover and relationship of the glycoproteins to each other and to HLA determinants. J Immunol. 1981 Sep;127(3):935–940. [PubMed] [Google Scholar]
- Helenius A. Alphavirus and flavivirus glycoproteins: structures and functions. Cell. 1995 Jun 2;81(5):651–653. doi: 10.1016/0092-8674(95)90523-5. [DOI] [PubMed] [Google Scholar]
- Hernandez L. D., Hoffman L. R., Wolfsberg T. G., White J. M. Virus-cell and cell-cell fusion. Annu Rev Cell Dev Biol. 1996;12:627–661. doi: 10.1146/annurev.cellbio.12.1.627. [DOI] [PubMed] [Google Scholar]
- Hirano A., Ayata M., Wang A. H., Wong T. C. Functional analysis of matrix proteins expressed from cloned genes of measles virus variants that cause subacute sclerosing panencephalitis reveals a common defect in nucleocapsid binding. J Virol. 1993 Apr;67(4):1848–1853. doi: 10.1128/jvi.67.4.1848-1853.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Januszeski M. M., Cannon P. M., Chen D., Rozenberg Y., Anderson W. F. Functional analysis of the cytoplasmic tail of Moloney murine leukemia virus envelope protein. J Virol. 1997 May;71(5):3613–3619. doi: 10.1128/jvi.71.5.3613-3619.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katayama Y., Hotta H., Nishimura A., Tatsuno Y., Homma M. Detection of measles virus nucleoprotein mRNA in autopsied brain tissues. J Gen Virol. 1995 Dec;76(Pt 12):3201–3204. doi: 10.1099/0022-1317-76-12-3201. [DOI] [PubMed] [Google Scholar]
- Kristensson K., Norrby E. Persistence of RNA viruses in the central nervous system. Annu Rev Microbiol. 1986;40:159–184. doi: 10.1146/annurev.mi.40.100186.001111. [DOI] [PubMed] [Google Scholar]
- 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]
- Radecke F., Spielhofer P., Schneider H., Kaelin K., Huber M., Dötsch C., Christiansen G., Billeter M. A. Rescue of measles viruses from cloned DNA. EMBO J. 1995 Dec 1;14(23):5773–5784. doi: 10.1002/j.1460-2075.1995.tb00266.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rall G. F., Manchester M., Daniels L. R., Callahan E. M., Belman A. R., Oldstone M. B. A transgenic mouse model for measles virus infection of the brain. Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4659–4663. doi: 10.1073/pnas.94.9.4659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rolls M. M., Webster P., Balba N. H., Rose J. K. Novel infectious particles generated by expression of the vesicular stomatitis virus glycoprotein from a self-replicating RNA. Cell. 1994 Nov 4;79(3):497–506. doi: 10.1016/0092-8674(94)90258-5. [DOI] [PubMed] [Google Scholar]
- Russell P. H., Almeida J. D. A regular subunit pattern seen on non-infectious Newcastle disease virus particles. J Gen Virol. 1984 Jun;65(Pt 6):1023–1031. doi: 10.1099/0022-1317-65-6-1023. [DOI] [PubMed] [Google Scholar]
- Sanderson C. M., Avalos R., Kundu A., Nayak D. P. Interaction of Sendai viral F, HN, and M proteins with host cytoskeletal and lipid components in Sendai virus-infected BHK cells. Virology. 1995 Jun 1;209(2):701–707. doi: 10.1006/viro.1995.1308. [DOI] [PubMed] [Google Scholar]
- Schmid A., Spielhofer P., Cattaneo R., Baczko K., ter Meulen V., Billeter M. A. Subacute sclerosing panencephalitis is typically characterized by alterations in the fusion protein cytoplasmic domain of the persisting measles virus. Virology. 1992 Jun;188(2):910–915. doi: 10.1016/0042-6822(92)90552-z. [DOI] [PubMed] [Google Scholar]
- Spielhofer P., Bächi T., Fehr T., Christiansen G., Cattaneo R., Kaelin K., Billeter M. A., Naim H. Y. Chimeric measles viruses with a foreign envelope. J Virol. 1998 Mar;72(3):2150–2159. doi: 10.1128/jvi.72.3.2150-2159.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Udem S. A. Measles virus: conditions for the propagation and purification of infectious virus in high yield. J Virol Methods. 1984 Feb;8(1-2):123–136. doi: 10.1016/0166-0934(84)90046-6. [DOI] [PubMed] [Google Scholar]
- Wilk T., Pfeiffer T., Bosch V. Retained in vitro infectivity and cytopathogenicity of HIV-1 despite truncation of the C-terminal tail of the env gene product. Virology. 1992 Jul;189(1):167–177. doi: 10.1016/0042-6822(92)90692-i. [DOI] [PubMed] [Google Scholar]
- van Binnendijk R. S., van der Heijden R. W., Osterhaus A. D. Monkeys in measles research. Curr Top Microbiol Immunol. 1995;191:135–148. doi: 10.1007/978-3-642-78621-1_9. [DOI] [PubMed] [Google Scholar]