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J Virol. Mar 1993; 67(3): 1493–1502.
PMCID: PMC237519

Cell fusion by the envelope glycoproteins of persistent measles viruses which caused lethal human brain disease.

Abstract

Measles virus (MV) rarely induces lethal diseases of the human central nervous system characterized by reduced expression of the viral envelope proteins and by lack of viral budding. The MV envelope contains two integral membrane proteins, termed fusion (F) protein and hemagglutinin (H) protein, and a membrane-associated matrix (M) protein. Previously, analysis of MV genes from autopsy material indicated that the M protein and the F protein intracellular domain are often drastically altered by mutations. Here, we present evidence that truncation of the F protein intracellular domain does not impair fusion function, and we suggest that this alteration interferes with viral budding. Unexpectedly, certain combinations of functional F and H proteins were unable to induce syncytium formation, an observation suggesting that specific F-H protein interactions are required for cell fusion. We also found that three of four H proteins of persistent MVs are defective in intracellular transport, oligosaccharide modification, dimerization, and fusion helper function. Thus, MVs replicating in the brain at the terminal stage of infection are typically defective in M protein and in the two integral membrane proteins. Whereas the M protein appears dispensable altogether, partial preservation of F-protein function and H-protein function seems to be required, presumably to allow local cell fusion. Certain subtle alterations of the F and H proteins may be instrumental for disease development.

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These references are in PubMed. This may not be the complete list of references from this article.
  • Baczko K, Liebert UG, 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. [PMC free article] [PubMed]
  • Bloom BR. Vaccines for the Third World. Nature. 1989 Nov 9;342(6246):115–120. [PubMed]
  • Bonner WM, Laskey RA. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. [PubMed]
  • Buckland R, Malvoisin E, Beauverger P, Wild F. A leucine zipper structure present in the measles virus fusion protein is not required for its tetramerization but is essential for fusion. J Gen Virol. 1992 Jul;73(Pt 7):1703–1707. [PubMed]
  • Cattaneo R, Billeter MA. Mutations and A/I hypermutations in measles virus persistent infections. Curr Top Microbiol Immunol. 1992;176:63–74. [PubMed]
  • Cattaneo R, Rebmann G, Baczko K, ter Meulen V, Billeter MA. Altered ratios of measles virus transcripts in diseased human brains. Virology. 1987 Oct;160(2):523–526. [PubMed]
  • Cattaneo R, Schmid A, Billeter MA, Sheppard RD, Udem SA. 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. [PMC free article] [PubMed]
  • Cattaneo R, Schmid A, Eschle D, Baczko K, ter Meulen V, Billeter MA. Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell. 1988 Oct 21;55(2):255–265. [PubMed]
  • Cattaneo R, Schmid A, Spielhofer P, Kaelin K, Baczko K, ter Meulen V, Pardowitz J, Flanagan S, Rima BK, Udem SA, et al. Mutated and hypermutated genes of persistent measles viruses which caused lethal human brain diseases. Virology. 1989 Dec;173(2):415–425. [PubMed]
  • Dotti CG, Simons K. Polarized sorting of viral glycoproteins to the axon and dendrites of hippocampal neurons in culture. Cell. 1990 Jul 13;62(1):63–72. [PubMed]
  • Dunphy WG, Rothman JE. Compartmental organization of the Golgi stack. Cell. 1985 Aug;42(1):13–21. [PubMed]
  • Fuerst TR, Niles EG, Studier FW, Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122–8126. [PMC free article] [PubMed]
  • Graves MC. Measles virus polypeptides in infected cells studied by immune precipitation and one-dimensional peptide mapping. J Virol. 1981 Apr;38(1):224–230. [PMC free article] [PubMed]
  • Hall WW, Lamb RA, Choppin PW. 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. [PMC free article] [PubMed]
  • Hirano A. Subacute sclerosing panencephalitis virus dominantly interferes with replication of wild-type measles virus in a mixed infection: implication for viral persistence. J Virol. 1992 Apr;66(4):1891–1898. [PMC free article] [PubMed]
  • Horvath CM, Paterson RG, Shaughnessy MA, Wood R, Lamb RA. Biological activity of paramyxovirus fusion proteins: factors influencing formation of syncytia. J Virol. 1992 Jul;66(7):4564–4569. [PMC free article] [PubMed]
  • Hu XL, Ray R, Compans RW. Functional interactions between the fusion protein and hemagglutinin-neuraminidase of human parainfluenza viruses. J Virol. 1992 Mar;66(3):1528–1534. [PMC free article] [PubMed]
  • Hurtley SM, Helenius A. Protein oligomerization in the endoplasmic reticulum. Annu Rev Cell Biol. 1989;5:277–307. [PubMed]
  • Ju G, Birrer M, Udem S, Bloom BR. Complementation analysis of measles virus mutants isolated from persistently infected lymphoblastoid cell lines. J Virol. 1980 Mar;33(3):1004–1012. [PMC free article] [PubMed]
  • Kohama T, Sato TA, Kobune F, Sugiura A. Maturation of measles virus hemagglutinin glycoprotein. Arch Virol. 1985;85(3-4):257–268. [PubMed]
  • Kornfeld R, Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem. 1985;54:631–664. [PubMed]
  • Kristensson K, Norrby E. Persistence of RNA viruses in the central nervous system. Annu Rev Microbiol. 1986;40:159–184. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Machamer CE, Rose JK. Influence of new glycosylation sites on expression of the vesicular stomatitis virus G protein at the plasma membrane. J Biol Chem. 1988 Apr 25;263(12):5948–5954. [PubMed]
  • Morrison T, McQuain C, McGinnes L. Complementation between avirulent Newcastle disease virus and a fusion protein gene expressed from a retrovirus vector: requirements for membrane fusion. J Virol. 1991 Feb;65(2):813–822. [PMC free article] [PubMed]
  • Moscona A, Peluso RW. Fusion properties of cells persistently infected with human parainfluenza virus type 3: participation of hemagglutinin-neuraminidase in membrane fusion. J Virol. 1991 Jun;65(6):2773–2777. [PMC free article] [PubMed]
  • Mulligan MJ, Yamshchikov GV, Ritter GD, Jr, Gao F, Jin MJ, Nail CD, Spies CP, Hahn BH, Compans RW. Cytoplasmic domain truncation enhances fusion activity by the exterior glycoprotein complex of human immunodeficiency virus type 2 in selected cell types. J Virol. 1992 Jun;66(6):3971–3975. [PMC free article] [PubMed]
  • Ng DT, Hiebert SW, Lamb RA. Different roles of individual N-linked oligosaccharide chains in folding, assembly, and transport of the simian virus 5 hemagglutinin-neuraminidase. Mol Cell Biol. 1990 May;10(5):1989–2001. [PMC free article] [PubMed]
  • Ng DT, Randall RE, Lamb RA. Intracellular maturation and transport of the SV5 type II glycoprotein hemagglutinin-neuraminidase: specific and transient association with GRP78-BiP in the endoplasmic reticulum and extensive internalization from the cell surface. J Cell Biol. 1989 Dec;109(6 Pt 2):3273–3289. [PMC free article] [PubMed]
  • Norrby E, Kristensson K, Brzosko WJ, Kapsenberg JG. 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. [PMC free article] [PubMed]
  • Ogura H, Sato H, Kamiya S, Nakamura S. Glycosylation of measles virus haemagglutinin protein in infected cells. J Gen Virol. 1991 Nov;72(Pt 11):2679–2684. [PubMed]
  • Oldstone MB. Viral persistence. Cell. 1989 Feb 24;56(4):517–520. [PubMed]
  • Pfeffer SR, Rothman JE. Biosynthetic protein transport and sorting by the endoplasmic reticulum and Golgi. Annu Rev Biochem. 1987;56:829–852. [PubMed]
  • Richardson C, Hull D, Greer P, Hasel K, Berkovich A, Englund G, Bellini W, Rima B, Lazzarini R. The nucleotide sequence of the mRNA encoding the fusion protein of measles virus (Edmonston strain): a comparison of fusion proteins from several different paramyxoviruses. Virology. 1986 Dec;155(2):508–523. [PubMed]
  • Rose JK, Bergmann JE. Expression from cloned cDNA of cell-surface secreted forms of the glycoprotein of vesicular stomatitis virus in eucaryotic cells. Cell. 1982 Oct;30(3):753–762. [PubMed]
  • Rose JK, Bergmann JE. Altered cytoplasmic domains affect intracellular transport of the vesicular stomatitis virus glycoprotein. Cell. 1983 Sep;34(2):513–524. [PubMed]
  • Rose JK, Buonocore L, Whitt MA. A new cationic liposome reagent mediating nearly quantitative transfection of animal cells. Biotechniques. 1991 Apr;10(4):520–525. [PubMed]
  • Rose JK, Doms RW. Regulation of protein export from the endoplasmic reticulum. Annu Rev Cell Biol. 1988;4:257–288. [PubMed]
  • Rota JS, Hummel KB, Rota PA, Bellini WJ. Genetic variability of the glycoprotein genes of current wild-type measles isolates. Virology. 1992 May;188(1):135–142. [PubMed]
  • Schmid A, Cattaneo R, Billeter MA. A procedure for selective full length cDNA cloning of specific RNA species. Nucleic Acids Res. 1987 May 26;15(10):3987–3996. [PMC free article] [PubMed]
  • Schmid A, Spielhofer P, Cattaneo R, Baczko K, ter Meulen V, Billeter MA. 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. [PubMed]
  • Schneider-Schaulies S, Liebert UG, Baczko K, Cattaneo R, Billeter M, ter Meulen V. Restriction of measles virus gene expression in acute and subacute encephalitis of Lewis rats. Virology. 1989 Aug;171(2):525–534. [PubMed]
  • Sheppard RD, Raine CS, Bornstein MB, Udem SA. 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. [PMC free article] [PubMed]
  • Sheshberadaran H, Chen SN, Norrby E. Monoclonal antibodies against five structural components of measles virus. I. Characterization of antigenic determinants on nine strains of measles virus. Virology. 1983 Jul 30;128(2):341–353. [PubMed]
  • Sheshberadaran H, Norrby E. Characterization of epitopes on the measles virus hemagglutinin. Virology. 1986 Jul 15;152(1):58–65. [PubMed]
  • Shimizu H, Hasebe F, Tsuchie H, Morikawa S, Ushijima H, Kitamura T. Analysis of a human immunodeficiency virus type 1 isolate carrying a truncated transmembrane glycoprotein. Virology. 1992 Aug;189(2):534–546. [PubMed]
  • Steinhauer DA, Holland JJ. Rapid evolution of RNA viruses. Annu Rev Microbiol. 1987;41:409–433. [PubMed]
  • Taylor J, Pincus S, Tartaglia J, Richardson C, Alkhatib G, Briedis D, Appel M, Norton E, Paoletti E. Vaccinia virus recombinants expressing either the measles virus fusion or hemagglutinin glycoprotein protect dogs against canine distemper virus challenge. J Virol. 1991 Aug;65(8):4263–4274. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Udem SA. Measles virus: conditions for the propagation and purification of infectious virus in high yield. J Virol Methods. 1984 Feb;8(1-2):123–136. [PubMed]
  • Varsanyi TM, Jörnvall H, Norrby E. Isolation and characterization of the measles virus F1 polypeptide: comparison with other paramyxovirus fusion proteins. Virology. 1985 Nov;147(1):110–117. [PubMed]
  • Wechsler SL, Fields BN. Differences between the intracellular polypeptides of measles and subacute sclerosing panencephalitis virus. Nature. 1978 Mar 30;272(5652):458–460. [PubMed]
  • Wechsler SL, Meissner HC. Measles and SSPE viruses: similarities and differences. Prog Med Virol. 1982;28:65–95. [PubMed]
  • Whitt MA, Chong L, Rose JK. Glycoprotein cytoplasmic domain sequences required for rescue of a vesicular stomatitis virus glycoprotein mutant. J Virol. 1989 Sep;63(9):3569–3578. [PMC free article] [PubMed]
  • Wild TF, Malvoisin E, Buckland R. Measles virus: both the haemagglutinin and fusion glycoproteins are required for fusion. J Gen Virol. 1991 Feb;72(Pt 2):439–442. [PubMed]
  • 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. [PubMed]
  • Wong TC, 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. [PMC free article] [PubMed]
  • Wong TC, Ayata M, Ueda S, Hirano A. Role of biased hypermutation in evolution of subacute sclerosing panencephalitis virus from progenitor acute measles virus. J Virol. 1991 May;65(5):2191–2199. [PMC free article] [PubMed]

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