Functional and nonfunctional measles virus matrix genes from lethal human brain infections.
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.
Ballart
I
I
Institut für Molekularbiologie I, Universität Zürich, Switzerland.
Huber
M
M
Schmid
A
A
Cattaneo
R
R
Billeter
M A
MA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000737:chemistry; D005814:Genes, Viral; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008459:Measles virus / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D013190:SSPE Virus / Q000235:genetics* / Q000302:isolation & purification; D013344:Subacute Sclerosing Panencephalitis / Q000382:microbiology* / Q000473:pathology; D014763:Viral Matrix Proteins / Q000235:genetics*
D004279:DNA, Viral; D006023:Glycoproteins; D014763:Viral Matrix Proteins; C023587:protein M (glycoprotein)