Fitness selection of hyperfusogenic measles virus F proteins associated with neuropathogenic phenotypes
Satoshi Ikegame, Takao Hashiguchi, Chuan-Tien Hung, Kristina Dobrindt, Kristen Brennand, Makoto Takeda, Benhur Lee
Abstract
Significance Measles remains a major cause of infant death globally. On rare occasions, measles virus infection of the central nervous system (CNS) leads to a fatal progressive inflammation of the brain many years after the initial infection. MeV isolates from such CNS infections harbors fusion (F) protein mutations that result in a hyperfusogenic phenotype. The small number of hyperfusogenic MeV-F mutants identified thus far limits our ability to understand how these mutations are selected in the context of CNS infections. We performed a saturating mutagenesis screen of MeV-F to identify a large set of mutants that would mimic the hyperfusogenic phenotype of MeV-F in CNS infections. Characterization of these mutants shed light on other paramyxoviruses known to establish chronic CNS infections.