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Unformatted text preview: JOURNAL OF VIROLOGY, Apr.1993,p.1848-1853 0022-538X/93/041848-06$02.00/0 Copyright 1993,American Societyfor Microbiology FunctionalAnalysisofMatrixProteinsExpressed from Cloned Genes ofMeasles VirusVariantsThat Cause Subacute SclerosingPanencephalitis Reveals a Common DefectinNucleocapsidBinding AKIKO HIRANO,* MINORU AYATA,t A N D Y H. WANG, A N D T I M O T H Y C. W O N G DepartmentofMicrobiology, UniversityofWashington Schoolof Medicine, Seattle, Washington 98195 Received 10November 1992/Accepted29 December 1992 We havedeveloped an invitronucleocapsid-bindingassayforstudyingthefunctionofthematrix (M)protein ofmeaslesvirus(MV) (A.Hirano,A. H.Wang,A.F.Gombart,andT.C.Wong, Proc.Natl.Acad. Sci. USA, 89:8745-8749,1992).Inthiscommunication we show thattheM proteinsofthreeM V strainsthatcause acute infection(Nagahata,Edmonston,andYN) bindefficientlytotheviralnucleocapsidswhereastheM proteinsof fourMV strainsisolatedfrom patientswith subacute sclerosingpanencephalitis(SSPE) (Biken,IP-3,Niigata, andYamagata) failtobindtotheviralnucleocapsids. M V Biken (anSSPE-related virus)producesvariantM sequences which encode two antigenicallydistinctforms of M protein. A serine-versus-leucine difference is responsiblefortheantigenicvariation.M V IP-3(anSSPE-relatedvirus)alsoproducesvariantM sequences, some ofwhich have been postulatedto encode a functional M protein responsiblefor the production ofan infectiousrevertantvirus.However, thevariantM proteinsofBiken and IP-3 strainsshow no nucleocapsid- binding activity. These results demonstrate that the nucleocapsid-binding function isconserved in the M proteinsofMV strainsthatcause acuteinfectionandthattheM proteinsofM V strainsthatcause SSPE exhibit a common defect in this function. Analysis of chimeric M proteins indicates that mutations in the amino-terminal, carboxy-proximal, or carboxy-terminal region ofthe M protein allabrogate nucleocapsid binding,suggestingthattheM proteinconformation is importantforinteractionwith theviralnucleocapsid. Subacute sclerosing panencephalitis (SSPE) is a fatal degenerative neurological disease caused by persistence of measlesvirus (MV) inthe centralnervous system (22).The virus isolatedfrom brains ofpatientswith SSPE by coculti- vation with cultured cells is typically defective in virion production. It spreads from cell to cell by inducing cell fusion (24).Early studies revealed that patientswith SSPE lackedantibodiesagainstthematrix(M)proteinof M V (11, 25),andM protein was not detectedinthebrainsofpatients withSSPEbyantibodiesagainstMV (9,10).SinceM protein playsan importantroleinparamyxovirus maturation(8),the apparent absence of M protein was hypothesized to be the cause of nonproductive infection by MV strainsthat cause SSPE (7)....
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