Functional and nonfunctional measles virus matrix genes from lethal human brain infections

Area of Science:

• Virology
• Neuroscience
• Genetics

Background:

• Subacute sclerosing panencephalitis (SSPE) is a rare, fatal neurological disease caused by persistent measles virus infection in the brain.
• The measles virus matrix (M) protein plays a critical role in viral assembly and release.

Purpose of the Study:

• To investigate the functionality of measles virus M genes derived from SSPE patients.
• To determine if mutations in the M gene contribute to the pathogenesis of SSPE.

Main Methods:

• Replaced the M gene of an infectious measles virus with M genes from four SSPE patients.
• Assessed viral replication and M protein function in cell culture.

Main Results:

• One of the four SSPE M genes was functionally competent, producing virus titers similar to controls.
• The other three SSPE M genes were nonfunctional, with inactivating mutations located in the carboxyl-terminal half of the M protein.
• Mutational alterations in the M gene were detected in 9 out of 10 SSPE cases.

Conclusions:

• Mutations leading to nonfunctional M protein are common in SSPE, suggesting a critical role in disease development.
• The presence of a functional M gene in one SSPE case indicates that M gene alteration may not be an absolute requirement for SSPE pathogenesis.