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

Author:

Angius Fabrizio12,Smuts Heidi3,Rybkina Ksenia12,Stelitano Debora12,Eley Brian45,Wilmshurst Jo65,Ferren Marion12,Lalande Alexandre7,Mathieu Cyrille12,Moscona Anne1289,Horvat Branka7ORCID,Hashiguchi Takao10,Porotto Matteo1211,Hardie Diana3

Affiliation:

1. Center for Host-Pathogen Interaction, Columbia University Medical Center, New York, New York, USA

2. Department of Pediatrics, Columbia University Medical Center, New York, New York, USA

3. Division of Medical Virology, Department of Pathology, University of Cape Town and National Health Laboratory Service, Cape Town, South Africa

4. Paediatric Infectious Diseases Unit, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa

5. Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

6. Paediatric Neurology Unit, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa

7. CIRI, International Center for Infectiology Research, Inserm, U1111, University Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Lyon, France

8. Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA

9. Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, New York, USA

10. Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan

11. Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, Italy

Abstract

Measles virus can invade the central nervous system (CNS) and cause severe neurological complications, such as MIBE and SSPE. However, mechanisms by which MeV enters the CNS and triggers the disease remain unclear. We analyzed viruses from brain tissue of individuals with MIBE or SSPE, infected during the same epidemic, after the onset of neurological disease. Our findings indicate that the emergence of hyperfusogenic MeV F proteins is associated with infection of the brain. We also demonstrate that hyperfusogenic F proteins permit MeV to enter cells and spread without the need to engage nectin-4 or CD150, known receptors for MeV that are not present on neural cells.

Funder

HHS | NIH | National Institute of Neurological Disorders and Stroke

Agence Nationale de la Recherche

Japan Agency for Medical Research and Development

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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