Analysis of a subacute sclerosing panencephalitis genotype B3 virus from the 2009-2010 South African measles epidemic shows that hyperfusogenic F proteins contribute to measles virus infection in the brain

Fabrizio Angius, Heidi Smuts, Ksenia Rybkina, Debora Stelitano, Brian Eley, Jo Wilmshurst, Marion Ferren, Alexandre Lalande, Cyrille Mathieu, Anne Moscona, Branka Horvat, Takao Hashiguchi, Matteo Porotto, Diana Hardie

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Abstract

During a measles virus (MeV) epidemic in 2009 in South Africa, measles inclusion body encephalitis (MIBE) was identified in several HIV-infected patients. Years later, children are presenting with subacute sclerosing panencephalitis (SSPE). To investigate the features of established MeV neuronal infections, viral sequences were analyzed from brain tissue samples of a single SSPE case and compared with MIBE sequences previously obtained from patients infected during the same epidemic. Both the SSPE and the MIBE viruses had amino acid substitutions in the ectodomain of the F protein that confer enhanced fusion properties. Functional analysis of the fusion complexes confirmed that both MIBE and SSPE F protein mutations promoted fusion with less dependence on interaction by the viral receptor-binding protein with known MeV receptors. While the SSPE F required the presence of a homotypic attachment protein, MeV H, in order to fuse, MIBE F did not. Both F proteins had decreased thermal stability compared to that of the corresponding wild-type F protein. Finally, recombinant viruses expressing MIBE or SSPE fusion complexes spread in the absence of known MeV receptors, with MIBE F-bearing viruses causing large syncytia in these cells. Our results suggest that alterations to the MeV fusion complex that promote fusion and cell-to-cell spread in the absence of known MeV receptors is a key property for infection of the brain.

Original languageEnglish
Article numbere0170018
JournalJournal of virology
Volume93
Issue number4
DOIs
Publication statusPublished - Feb 1 2019

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Angius, F., Smuts, H., Rybkina, K., Stelitano, D., Eley, B., Wilmshurst, J., Ferren, M., Lalande, A., Mathieu, C., Moscona, A., Horvat, B., Hashiguchi, T., Porotto, M., & Hardie, D. (2019). Analysis of a subacute sclerosing panencephalitis genotype B3 virus from the 2009-2010 South African measles epidemic shows that hyperfusogenic F proteins contribute to measles virus infection in the brain. Journal of virology, 93(4), [e0170018]. https://doi.org/10.1128/JVI.01700-18