Molecular Features of the Measles Virus Viral Fusion Complex That Favor Infection and Spread in the Brain
Cyrille Mathieu, Francesca T. Bovier, Marion Ferren, Nicole A. P. Lieberman, Camilla Predella, Alexandre Lalande, Vikas Peddu, Michelle J. Lin, Amin Addetia, Achchhe Patel, Victor K. Outlaw, Barbara Corneo, N. Valerio Dorrello, Thomas Briese, Diana Hardie, Branka Horvat, Anne Moscona, Alexander L. Greninger, Matteo Porotto
Abstract
Measles virus (MeV) infection can cause serious complications in immunocompromised individuals, including measles inclusion body encephalitis (MIBE). In some cases, MeV persistence and subacute sclerosing panencephalitis (SSPE), another severe central nervous system (CNS) complication, develop even in the face of a systemic immune response. Both MIBE and SSPE are relatively rare but lethal. It is unclear how MeV causes CNS infection. We introduced specific mutations that are found in MIBE or SSPE cases into the MeV fusion protein to test the hypothesis that dysregulation of the viral fusion complex-comprising F and the receptor binding protein, H-allows virus to spread in the CNS. Using metagenomic, structural, and biochemical approaches, we demonstrate that altered fusion properties of the MeV H-F fusion complex permit MeV to spread in brain tissue.