New Insights into Measles Virus Brain Infections. Issue 2 (February 2019)

• Record Type: Journal Article
• Authors: Watanabe, Shumpei; Shirogane, Yuta; Sato, Yuma; Hashiguchi, Takao; Yanagi, Yusuke
• Is Part Of: Trends in microbiology. Volume 27:Issue 2(2019)
• Page Start: 164
• Page End: 175
• Publication Date: 2019-02
• Subjects: measles virus -- SSPE -- MIBE -- fusion -- CNS -- paramyxovirus; Microbiology -- Periodicals; Infection -- Periodicals; Virulence (Microbiology) -- Periodicals; Infection -- Periodicals; Microbiology -- Periodicals; Virulence -- Periodicals; Microbiologie -- Périodiques; Infection -- Périodiques; Virulence (Microbiologie) -- Périodiques; Infection; Microbiology; Virulence (Microbiology); 579
• DOI: 10.1016/j.tim.2018.08.010
• Languages: English
• ISSNs: 0966-842X

Abstract

Abstract : Measles virus (MeV) may persist in the brain, causing fatal neurodegenerative diseases, subacute sclerosing panencephalitis, and measles inclusion-body encephalitis. However, the mechanism of MeV propagation in the brain remains unexplained because human neurons affected by the diseases do not express the known receptors for MeV. Recent studies have revealed that certain changes in the ectodomain of the MeV fusion (F) protein play a key role in MeV spread in the brain. These changes destabilize the prefusion form of the F protein and render it hyperfusogenic, which in turn allows the virus to propagate in neurons. Based on crystal structures of the F protein, effective fusion inhibitors could be developed to treat these diseases. Highlights: Measles virus (MeV), in rare cases, persists in the central nervous system and causes fatal neurodegenerative diseases. Human neurons do not express the known receptors for MeV (CD150 and nectin 4), and the mechanism of MeV propagation in the brain is unknown. The specific changes in the ectodomain of the MeV fusion (F) protein, rather than the defects in the matrix protein and the cytoplasmic tail of the F protein, play a key role in MeV spread in the brain. The changes in the ectodomain destabilize the prefusion form of the F protein and render it hyperfusogenic, which in turn allows MeV to propagate in neurons. The putative neuronal receptor for MeV may be required for the MeV attachment protein to trigger destabilized F proteins. Crystal structures of the F protein will serve as a structural template to develop more effective fusion inhibitors to treat MeV brain infections.