Key result
Specific mutations in the measles virus matrix protein (R293Q) and fusion protein (I225M) promoted progeny virion production, syncytia formation, and viral spread in rat brain slice cultures.
Why the study?
How measles virus enters the brain and persists in neuronal tissue is not fully understood.
Specific mutations in the measles virus matrix and fusion proteins enhance viral replication and neuro-invasion in an ex vivo rat brain model.
MV mutations' effects on titer and neuroinvasion in vitro warrant clinical caution; leaves open mechanisms of brain persistence.
Measles virus (MV) can cause severe acute diseases as well as long-lasting clinical deteriorations due to viral-induced immunosuppression and neuronal manifestation. How the virus enters the brain and manages to persist in neuronal tissue is not fully understood. Various mutations in the viral genes were found in MV strains isolated from patient brains. In this study, reverse genetics was used to introduce mutations in the fusion, matrix and polymerase genes of MV. The generated virus clones were characterized in cell culture and used to infect rat brain slice cultures. A mutation in the carboxy-terminal domain of the matrix protein (R293Q) promoted the production of progeny virions. This effect was observed in Vero cells irrespective of the expression of the signaling lymphocyte activation molecule (SLAM). Furthermore, a mutation in the fusion protein (I225M) induced syncytia formation on Vero cells in the absence of SLAM and promoted viral spread throughout the rat brain slices. In this study, a solid ex vivo model was established to elucidate the MV mutations contributing to neural manifestation.
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Busch et al. (2021) studied Measles virus infection. Mutations in the fusion, matrix and polymerase genes of Measles virus (e.g., R293Q, I225M) was evaluated on Viral titer, syncytia formation, and viral spread. Specific mutations in the measles virus matrix protein (R293Q) and fusion protein (I225M) promoted progeny virion production, syncytia formation, and viral spread in rat brain slice cultures.
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