Benjamin Beavington, University of Toronto

Benjamin Beavington (University of Toronto), Dr. Michael Norris (University of Toronto)

Building & Escaping

The global resurgence of measles fueled by declining immunization coverage, sustained outbreaks across multiple continents, and loss of elimination status in the Americas and Europe, has produced record case counts not seen in decades. Despite the severe complications of measles infection, no antiviral therapies are approved, leaving a critical gap in clinical management and public health response. The measles virus matrix protein is a multifunctional protein that serves as a central scaffold for virion assembly and budding at the plasma membrane. Beyond this established structural role, the matrix protein has been implicated in additional non-structural functions that contribute to efficient infection, yet these activities remain poorly characterized. To define host pathways targeted by the matrix protein, we performed complementary proximity-dependent biotin identification (BioID) and affinity purification–mass spectrometry (AP-MS). We identified 125 high-confidence host interactors, including 113 not previously reported for measles or any other paramyxovirus matrix protein. Functional enrichment and network analyses revealed overrepresentation of host proteins involved in cell adhesion, cytoskeletal organization, plasma membrane projections, clathrin-mediated cargo loading, and chromatin binding, indicating broader roles for the matrix protein in modulating host cellular architecture and signalling. Among these interactors, SRC, PIP4K2A, and BRD2 emerged as promising druggable candidates with potential to restrict viral replication. We are currently evaluating experimental and FDA-approved inhibitors targeting these proteins for their ability to suppress measles virus infection. Together, these results expand the measles virus matrix interactome, uncover host systems exploited during infection, and identify candidate targets for rapid antiviral development and drug repurposing.