The measles virus receptor SLAMF1 can mediate particle endocytosis

Journal article

The signalling lymphocyte activation molecule F1 (SLAMF1) is both a microbial sensor and entry receptor for Measles virus (MeV). Herein, we describe a new role for SLAMF1 to mediate MeV endocytosis that is in contrast with the alternative, and generally accepted, model that MeV genome enters cells only after fusion at the cell surface. We demonstrated that MeV engagement of SLAMF1 induces dramatic but transient morphological changes, most prominently in the formation of membrane blebs, which were shown to co-localise with incoming viral particles, and rearrangement of the actin cytoskeleton in infected cells. MeV infection was dependent on these dynamic cytoskeletal changes as well as fluid uptake through a macropinocytosis-like pathway as chemical inhibition of these processes inhibited entry. Moreover, we identified a role for the RhoA-ROCK-myosin-II signalling axis in this MeV internalisation process, highlighting a novel role for this recently characterised pathway in virus entry. Our study shows that MeV can hijack a microbial sensor normally involved in bacterial phagocytosis to drive endocytosis using a complex pathway that shares features with canonical viral macropinocytosis, phagocytosis and mechanotransduction. This uptake pathway is specific to SLAMF1-positive cells and occurs within 60 minutes of viral attachment. Measles remains a significant cause of mortality in human populations and this research sheds a new light on the very first steps of infection of this important pathogen.

Authors: Gonçalves-Carneiro, D; McKeating, J; Bailey, D

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Society for Microbiology
• Journal: Journal of Virology
• Volume: 91
• Issue: 7
• Pages: e02255-16
• Publication date: 2017-01-01
• Acceptance date: 2017-01-01
• DOI: 10.1128/JVI.02255-16
• EISSN: 1098-5514
• ISSN: 0022-538X
• Language: English
• Keywords: Journal Article