Abstract
Subacute sclerosing panencephalitis (SSPE) is a lethal disease induced by the persistence of measles virus in the human brain. In many SSPE cases, the viral matrix (M) protein cannot be detected; in others, M proteins of the expected size are found and sequence analysis of M cDNAs has confirmed that the reading frames are intact, showing only several missense mutations. To determine whether these alterations result in nonfunctional proteins, we have replaced the M gene of an infectious full-length genomic cDNA (from vaccine strain Edmonston) with different M genes derived from four patients with SSPE. One of the SSPE M genes tested proved to be functionally competent, giving rise to a virus yielding titers similar to those of viruses containing the M gene from control lytic strains. The other three SSPE M genes were not functionally competent in the same test. In all three cases, the inactivating changes resided in the carboxyl-terminal half of the M protein, as shown by the exchange of either of the two genes halves. In summary, mutational M gene alterations, which either prevent synthesis of M protein altogether or only allow synthesis of nonfunctional M protein, have been detected by us and by others in 9 of 10 SSPE cases. The one functional M gene appears to be an exception to the rule, indicating that M gene alteration might not be an absolute requirement for disease development.
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- Ayata M., Hirano A., Wong T. C. Structural defect linked to nonrandom mutations in the matrix gene of biken strain subacute sclerosing panencephalitis virus defined by cDNA cloning and expression of chimeric genes. J Virol. 1989 Mar;63(3):1162–1173. doi: 10.1128/jvi.63.3.1162-1173.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baczko K., Liebert U. G., Billeter M., Cattaneo R., Budka H., ter Meulen V. Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis. J Virol. 1986 Aug;59(2):472–478. doi: 10.1128/jvi.59.2.472-478.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baczko K., Liebert U. G., Cattaneo R., Billeter M. A., Roos R. P., ter Meulen V. Restriction of measles virus gene expression in measles inclusion body encephalitis. J Infect Dis. 1988 Jul;158(1):144–150. doi: 10.1093/infdis/158.1.144. [DOI] [PubMed] [Google Scholar]
- Ballart I., Eschle D., Cattaneo R., Schmid A., Metzler M., Chan J., Pifko-Hirst S., Udem S. A., Billeter M. A. Infectious measles virus from cloned cDNA. EMBO J. 1990 Feb;9(2):379–384. doi: 10.1002/j.1460-2075.1990.tb08121.x. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
- Bellini W. J., Englund G., Richardson C. D., Rozenblatt S., Lazzarini R. A. Matrix genes of measles virus and canine distemper virus: cloning, nucleotide sequences, and deduced amino acid sequences. J Virol. 1986 May;58(2):408–416. doi: 10.1128/jvi.58.2.408-416.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burnstein T., Jacobsen L. B., Zeman W., Chen T. T. Persistent infection of BSC-1 cells by defective measles virus derived from subacute sclerosing panencephalitis. Infect Immun. 1974 Dec;10(6):1378–1382. doi: 10.1128/iai.10.6.1378-1382.1974. [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., Schmid A., Billeter M. A., Sheppard R. D., Udem S. A. Multiple viral mutations rather than host factors cause defective measles virus gene expression in a subacute sclerosing panencephalitis cell line. J Virol. 1988 Apr;62(4):1388–1397. doi: 10.1128/jvi.62.4.1388-1397.1988. [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]
- Cattaneo R., Schmid A., Rebmann G., Baczko K., Ter Meulen V., Bellini W. J., Rozenblatt S., Billeter M. A. Accumulated measles virus mutations in a case of subacute sclerosing panencephalitis: interrupted matrix protein reading frame and transcription alteration. Virology. 1986 Oct 15;154(1):97–107. doi: 10.1016/0042-6822(86)90433-2. [DOI] [PubMed] [Google Scholar]
- Cattaneo R., Schmid A., Spielhofer P., Kaelin K., Baczko K., ter Meulen V., Pardowitz J., Flanagan S., Rima B. K., Udem S. A. Mutated and hypermutated genes of persistent measles viruses which caused lethal human brain diseases. Virology. 1989 Dec;173(2):415–425. doi: 10.1016/0042-6822(89)90554-0. [DOI] [PubMed] [Google Scholar]
- Cattaneo R., Will H., Schaller H. Hepatitis B virus transcription in the infected liver. EMBO J. 1984 Sep;3(9):2191–2196. doi: 10.1002/j.1460-2075.1984.tb02113.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dörries R., ter Meulen V. Specificity of IgM antibodies in acute human coxsackievirus B infections, analysed by indirect solid phase enzyme immunoassay and immunoblot technique. J Gen Virol. 1983 Jan;64(Pt 1):159–167. doi: 10.1099/0022-1317-64-1-159. [DOI] [PubMed] [Google Scholar]
- Elliott G. D., Afzal M. A., Martin S. J., Rima B. K. Nucleotide sequence of the matrix, fusion and putative SH protein genes of mumps virus and their deduced amino acid sequences. Virus Res. 1989 Jan;12(1):61–75. doi: 10.1016/0168-1702(89)90054-3. [DOI] [PubMed] [Google Scholar]
- Enami M., Sato T. A., Sugiura A. Matrix protein of cell-associated subacute sclerosing panencephalitis viruses. J Gen Virol. 1989 Aug;70(Pt 8):2191–2196. doi: 10.1099/0022-1317-70-8-2191. [DOI] [PubMed] [Google Scholar]
- Hall W. W., Choppin P. W. Measles-virus proteins in the brain tissue of patients with subacute sclerosing panencephalitis: absence of the M protein. N Engl J Med. 1981 May 7;304(19):1152–1155. doi: 10.1056/NEJM198105073041906. [DOI] [PubMed] [Google Scholar]
- Hall W. W., Lamb R. A., Choppin P. W. Measles and subacute sclerosing panencephalitis virus proteins: lack of antibodies to the M protein in patients with subacute sclerosing panencephalitis. Proc Natl Acad Sci U S A. 1979 Apr;76(4):2047–2051. doi: 10.1073/pnas.76.4.2047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kretz K. A., Carson G. S., O'Brien J. S. Direct sequencing from low-melt agarose with Sequenase. Nucleic Acids Res. 1989 Jul 25;17(14):5864–5864. doi: 10.1093/nar/17.14.5864. [DOI] [PMC free article] [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]
- Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
- Norrby E., Kristensson K., Brzosko W. J., Kapsenberg J. G. Measles virus matrix protein detected by immune fluorescence with monoclonal antibodies in the brain of patients with subacute sclerosing panencephalitis. J Virol. 1985 Oct;56(1):337–340. doi: 10.1128/jvi.56.1.337-340.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roos R. P., Graves M. C., Wollmann R. L., Chilcote R. R., Nixon J. Immunologic and virologic studies of measles inclusion body encephalitis in an immunosuppressed host: the relationship to subacute sclerosing panencephalitis. Neurology. 1981 Oct;31(10):1263–1270. doi: 10.1212/wnl.31.10.1263. [DOI] [PubMed] [Google Scholar]
- Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
- Schmid A., Cattaneo R., Billeter M. A. A procedure for selective full length cDNA cloning of specific RNA species. Nucleic Acids Res. 1987 May 26;15(10):3987–3996. doi: 10.1093/nar/15.10.3987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sheppard R. D., Raine C. S., Bornstein M. B., Udem S. A. Rapid degradation restricts measles virus matrix protein expression in a subacute sclerosing panencephalitis cell line. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7913–7917. doi: 10.1073/pnas.83.20.7913. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wechsler S. L., Fields B. N. Differences between the intracellular polypeptides of measles and subacute sclerosing panencephalitis virus. Nature. 1978 Mar 30;272(5652):458–460. doi: 10.1038/272458a0. [DOI] [PubMed] [Google Scholar]
- Wong T. C., Ayata M., Hirano A., Yoshikawa Y., Tsuruoka H., Yamanouchi K. Generalized and localized biased hypermutation affecting the matrix gene of a measles virus strain that causes subacute sclerosing panencephalitis. J Virol. 1989 Dec;63(12):5464–5468. doi: 10.1128/jvi.63.12.5464-5468.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

