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.
We have developed an in vitro nucleocapsid-binding assay for studying the function of the matrix (M) protein of measles virus (MV) (A. Hirano, A. H. Wang, A. F. Gombart, and T. C. Wong, Proc. Natl. Acad. Sci. USA, 89:8745-8749, 1992). In this communication we show that the M proteins of three MV strains that cause acute infection (Nagahata, Edmonston, and YN) bind efficiently to the viral nucleocapsids whereas the M proteins of four MV strains isolated from patients with subacute sclerosing panencephalitis (SSPE) (Biken, IP-3, Niigata, and Yamagata) fail to bind to the viral nucleocapsids. MV Biken (an SSPE-related virus) produces variant M sequences which encode two antigenically distinct forms of M protein. A serine-versus-leucine difference is responsible for the antigenic variation. MV IP-3 (an SSPE-related virus) also produces variant M sequences, some of which have been postulated to encode a functional M protein responsible for the production of an infectious revertant virus. However, the variant M proteins of Biken and IP-3 strains show no nucleocapsid-binding activity. These results demonstrate that the nucleocapsid-binding function is conserved in the M proteins of MV strains that cause acute infection and that the M proteins of MV strains that cause 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 of the M protein all abrogate nucleocapsid binding, suggesting that the M protein conformation is important for interaction with the viral nucleocapsid.
Hirano
A
A
Department of Microbiology, University of Washington School of Medicine, Seattle 98195.
Ayata
M
M
Wang
A H
AH
Wong
T C
TC
D000956:Antigens, Viral / Q000235:genetics; D002213:Capsid / Q000378:metabolism; D003001:Cloning, Molecular; D005814:Genes, Viral; D006801:Humans; D066298:In Vitro Techniques; D008459:Measles virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D013344:Subacute Sclerosing Panencephalitis / Q000382:microbiology*; D014758:Viral Core Proteins / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics
D000956:Antigens, Viral; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; D015678:Viral Structural Proteins