TY - JOUR
T1 - Functional and nonfunctional measles virus matrix genes from lethal human brain infections
AU - Ballart, I.
AU - Huber, M.
AU - Schmid, A.
AU - Cattaneo, R.
AU - Billeter, M. A.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1991
Y1 - 1991
N2 - 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 gene 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.
AB - 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 gene 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.
UR - http://www.scopus.com/inward/record.url?scp=0026058682&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026058682&partnerID=8YFLogxK
U2 - 10.1128/jvi.65.6.3161-3166.1991
DO - 10.1128/jvi.65.6.3161-3166.1991
M3 - Article
C2 - 2033668
AN - SCOPUS:0026058682
VL - 65
SP - 3161
EP - 3166
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 6
ER -