Abstract
Measles virus (MV) replication in brain tissue of Lewis rats with acute (AE) and subacute (SAME) encephalitis was characterized by biochemical techniques. Messenger RNAs specific for measles virus nucleocapsid (N), phospho (P)-, matrix (M), fusion (F), and haemagglutinin (H) protein were detected in all brain extracts examined. The quantity of the individual MV mRNA species was quite different in comparison to lytically infected Vero cells. A steep gradient of MV transcripts was found in brain tissue which is most likely due to strongly attenuated transcription of mRNAs along the viral genome, representing particularly low transcription of the glycoprotein genes. In addition, in vitro translation assays only revealed synthesis of N and P protein in consistent fashion. The mRNAs for the glycoproteins did not direct the synthesis of detectable viral proteins whereas the M mRNA revealed some activity in animals with AE. The data indicate a strong restriction of the MV envelope gene expression in infected brain tissue, which is independent of the incubation time and type of the central nervous system (CNS) disease. This phenomenon which is similar to the findings observed in measles inclusion body encephalitis and subacute sclerosing panencephalitis suggest that host factors may initially be responsible for the initiation of transcriptional and translational alterations.
References
- Baczko K., Carter M.J., Billeter M., ter Meulen V. Measles virus gene expression in subacute sclerosing panencephalitis. Virus Res. 1984;1:585–595. doi: 10.1016/0168-1702(84)90015-7. [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;59:472–478. 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;158:144–150. doi: 10.1093/infdis/158.1.144. [DOI] [PubMed] [Google Scholar]
- 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;58:408–416. doi: 10.1128/jvi.58.2.408-416.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Billeter M., Baczko K., Schmid A., ter Meulen V. Cloning of DNA Corresponding to four different measles virus genomic regions. Virology. 1984;132:149–159. doi: 10.1016/0042-6822(84)90099-0. [DOI] [PubMed] [Google Scholar]
- Blumberg B.M., Rose K., Simona M.G., Roux L., Giorgi C., Kolakofsky D. Analysis of the Sendai virus M gene and protein. J. Virol. 1984;52:656–663. doi: 10.1128/jvi.52.2.656-663.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brawerman G. Determinants of Messenger RNA Stability. Cell. 1987;48:5–6. doi: 10.1016/0092-8674(87)90346-1. [DOI] [PubMed] [Google Scholar]
- Buckland R., Gerald C., Barker R., Wild T.F. Fusion glycoprotein of measles virus: Nucleotide sequence of the gene and comparison with other paramyxoviruses. J. Gen. Virol. 1987;68:1695–1703. doi: 10.1099/0022-1317-68-6-1695. [DOI] [PubMed] [Google Scholar]
- Carter M.J., Willcocks M.M., Löffler S., ter Meulen V. Relationships between monoclonal antibody binding sites on the measles virus haemagglutinin. J. Gen. Virol. 1982;63:113–120. doi: 10.1099/0022-1317-63-1-113. [DOI] [PubMed] [Google Scholar]
- Cattaneo R., Kaelin K., Baczko K., Billeter M.A. Measles virus editing provides an additional cystein-rich protein. Cell. 1989;56:759–764. doi: 10.1016/0092-8674(89)90679-x. [DOI] [PubMed] [Google Scholar]
- Cattaneo R., Rebmann G., Baczko K., ter Meulen V., Billeter M.A. Altered ratios of measles virus transcripts in diseased human brains. Virology. 1987;160:523–526. doi: 10.1016/0042-6822(87)90031-6. [DOI] [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 diseased human brain. EMBO J. 1987;6:681–687. doi: 10.1002/j.1460-2075.1987.tb04808.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cattaneo R., Schmid A., Eschle D., Baczko K., Baczko K., ter Meulen V., Billeter M.A. Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell. 1988;55:255–265. 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 proteins reading frame and transcription alteration. Virology. 1986;154:97–107. doi: 10.1016/0042-6822(86)90433-2. [DOI] [PubMed] [Google Scholar]
- Chirgwin J.M., Przybyla A.E., Macdonald R.J., Rutter W.J. Isolation of biologically active ribonucleic acids from sources enriched in ribonuclease. Biochemistry. 1979;18:5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Cox K.H., DeLeon D.V., Angerer L.M., Angerer R.C. Detection of mRNAs in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev. Biol. 1984;101:485–502. doi: 10.1016/0012-1606(84)90162-3. [DOI] [PubMed] [Google Scholar]
- Davis L.G., Dibner M.D., Battey J.R. Elsevier; New York/Amsterdam/London: 1986. Basic Methods in Molecular Biology. [Google Scholar]
- Domingo E., Holland J.J. High error rates, population equilibrium and evolution of RNA replication systems. In: Domingo E., Ahlquist P., Holland J.J., editors. RNA Genetics. CRC Press; Boca Raton, FL: 1987. [Google Scholar]
- Dörries R., Liebert U.G., ter Meulen V. Comparative analysis of virus-specific antibodies and immunoglobulins in serum and cerebrospinal fluid of subacute measles virus induced encephalomyelitis (SAME) in rats and subacute sclerosing panencephalitis (SSPE) J. Neuroimmunol. 1988;19:339–352. doi: 10.1016/0165-5728(88)90014-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Favaloro J.R., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: Analysis by two-dimensional nuclease S1 gel mapping. In: Grossman L., Maldave K., editors. Vol. 65. Academic Press; New York: 1980. pp. 718–749. (Methods in Enzymology). [DOI] [PubMed] [Google Scholar]
- Greer P.A., Hasel K.W., Millward S. Cloning and in vitro expression of the measles virus matrix gene. Biochem. Cell Biol. 1986;64:1038–1043. doi: 10.1139/o86-137. [DOI] [PubMed] [Google Scholar]
- Haase A.T., Brahic M., Stowing L., Beuth H. Vol. 7. Academic Press; San Diego: 1984. Detection of viral nucleic acids by in situ hybridization; pp. 189–226. (Methods in Virology). [Google Scholar]
- Hidaka Y., Kanda Y., Iwasaki K., Nomoto A., Shioda T., Shibuta H. Nucleotide sequence of a Sendai virus genome region covering the entire M gene and the 3′ proximal 1013 nucleotides of the F gene. Nucleic Acids Res. 1984;12:7965–7973. doi: 10.1093/nar/12.21.7965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horikami S.M., Moyer S.A. Vol. 79. 1982. Host range mutants of VSV defective in in vitro RNA methylation; pp. 7694–7698. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
- Joseph B.S., Lampert P.W., Oldstone M.B.A. Replication and persistence of measles virus in defined subpopulations of human leukocytes. J. Virol. 1975;16:1638–1649. doi: 10.1128/jvi.16.6.1638-1649.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liebert U.G., Baczko K., Budka H., ter Meulen V. Restricted expression of measles virus proteins in brains from cases of subacute sclerosing panencephalitis. J. Gen. Virol. 1986;67:2435–2444. doi: 10.1099/0022-1317-67-11-2435. [DOI] [PubMed] [Google Scholar]
- Liebert U.G., ter Meulen V. Virological aspects of measles virus induced encephalomyelitis in Lewis and BN rats. J. Gen. Virol. 1987;68:1715–1722. doi: 10.1099/0022-1317-68-6-1715. [DOI] [PubMed] [Google Scholar]
- Lucas C.J., Ubels-Postma J.C., Rezee A., Galama J.M.D. Activation of measles virus from silently infected human lymphocytes. J. Exp. Med. 1978;148:940–952. doi: 10.1084/jem.148.4.940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McChesney M.B., Kehrl J.H., Valsamakis A., Fauci A.S., Oldstone M.B.A. Measles virus infection of B lymphocytes permits cellular activation but blocks progression through the cell cycle. J. Virol. 1987;61:3441–3447. doi: 10.1128/jvi.61.11.3441-3447.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ter Meulen V., Carter M.J. Morbillivirus persistent infections in animals and man. In: Mahy B.W.J., Minson A.C., Darby G.K., editors. Virus Persistence. Cambridge Univ. Press; London/New York: 1982. pp. 97–132. [Google Scholar]
- Miller C.A., Carrigan D.R. Vol. 79. 1982. Reversible repression and activation of measles virus infection in neural cells; pp. 1629–1633. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ogura H., Baczko K., Rima B.K., ter Meulen V. Selective inhibition of translation of the mRNA coding for the measles virus membrane protein at elevated temperatures. J. Virol. 1987;61:472–479. doi: 10.1128/jvi.61.2.472-479.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ogura H., Rima B.K., ter Meulen V. Restricted synthesis of the fusion protein of measles virus at elevated temperatures. J. Gen. Virol. 1988;69:925–929. doi: 10.1099/0022-1317-69-4-925. [DOI] [PubMed] [Google Scholar]
- Ordahl C.P., Evans G.L., Cooper T.A., Kunz G., Perriard J.C. Complete cDNA-derived amino acid sequence of chick muscle creatine kinase. J. Biol. Chem. 1984;259:15,224–15,227. [PubMed] [Google Scholar]
- Pontecorvi A., Tata J.R., Phyillaier M., Robbins J. Selective degradation of mRNA: The role of short-lived proteins in differential destabilization of insulin-induced creatine phosphokinase and myosin heavy chain mRNAs during rat skeletal muscle L6 cell differentiation. EMBO J. 1988;7(5):1489–1495. doi: 10.1002/j.1460-2075.1988.tb02967.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robbins S.J., Rapp F. Inhibition of measles virus replication by cAMP. Virology. 1980;106:317–326. doi: 10.1016/0042-6822(80)90255-x. [DOI] [PubMed] [Google Scholar]
- Rozenblatt S., Koch T., Pinhasi O., Bratasin S. Infective substructures of measles virus from acutely and persistently infected cells. J. Virol. 1979;32:329–333. doi: 10.1128/jvi.32.1.329-333.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sap J., Munoz A., Damm K., Goldberg Y., Ghysdael J., Leutz A., Beng H., Vennstrom B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature (London) 1986;324:635–640. doi: 10.1038/324635a0. [DOI] [PubMed] [Google Scholar]
- Steinhauer D.A., Holland J.J. Rapid evolution of RNA viruses. Annu. Rev. Microbiol. 1987;41:409–433. doi: 10.1146/annurev.mi.41.100187.002205. [DOI] [PubMed] [Google Scholar]
- Takeishi K., Kaneda S., Aysusawa D., Shimizu K., Gotoh O., Seno T. Nucleotide sequence of a functional cDNA for human thymidylate synthase. Nucleic Acids Res. 1985;13:2035–2043. doi: 10.1093/nar/13.6.2035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas S.M., Lamb R.A., Paterson R.G. Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5. Cell. 1988;54:891–902. doi: 10.1016/S0092-8674(88)91285-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wong T.C., Wipf G., Hirano A. The measles virus matrix gene and gene product defined by in vitro and in vivo expression. Virology. 1987;157:497–508. doi: 10.1016/0042-6822(87)90292-3. [DOI] [PubMed] [Google Scholar]
- Yoshikawa Y., Yamanouchi K. Effects of papaverine treatment on replication of measles virus in human neural and non-neural cells. J. Virol. 1984;50:489–496. doi: 10.1128/jvi.50.2.489-496.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]