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bioRxiv · 10.1101/761502

A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion

Chan, K. M. C.·Son, S.·Schmid, E. M.·Fletcher, D. A.
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Abstract

Cell-cell fusion, which is essential for tissue development and used by some viruses to form pathological syncytia, is typically driven by fusogenic membrane proteins with tall (>10 nm) ectodomains that undergo conformational changes to bring apposing membranes in close contact prior to fusion. Here we report that a viral fusogen with a short (<2 nm) ectodomain, the reptilian orthoreovirus p14, accomplishes the same task by hijacking the actin cytoskeleton. We show that the cytoplasmic domain of p14 triggers N-WASP-mediated assembly of a branched actin network, directly coupling local force generation with a short membrane-disruptive ectodomain. This work reveals that overcoming energetic barriers to cell-cell fusion does not require conformational changes of tall fusogens but can instead be driven by harnessing the host cytoskeleton.\n\nImpact StatementA viral fusogen drives cell-cell fusion by hijacking the actin machinery to directly couple actin assembly with a short fusogenic ectodomain.

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Chan, K. M. C., Son, S., Schmid, E. M., Fletcher, D. A.. 2019-09-08. A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion. https://doi.org/10.1101/761502

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