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bioRxiv · 10.1101/2022.03.12.484076

Visualization of conformational changes and membrane remodeling leading to genome delivery by viral class-II fusion machinery

Mangala Prasad, V.·Blijleven, J. S.·Smit, J. M.·Lee, K. K.
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Abstract

Chikungunya virus (CHIKV) is a human pathogen that delivers its genome to the host cell cytoplasm through endocytic low pH-activated membrane fusion mediated by class-II fusion proteins. Though structures of prefusion, icosahedral CHIKV are available, structural characterization of virion interaction with membranes has been limited. Here, we have used cryo-electron tomography to visualize CHIKVs complete membrane fusion pathway, identifying key intermediary glycoprotein conformations coupled to membrane remodeling events. Using sub-tomogram averaging, we elucidate features of the low pH-exposed virion, nucleocapsid and full-length E1-glycoproteins post-fusion structure. Contrary to class-I fusion systems, CHIKV achieves membrane apposition by protrusion of extended E1-glycoprotein homotrimers into the target membrane. The fusion process also features a large hemifusion diaphragm that transitions to a wide pore for intact nucleocapsid delivery. Our analyses provide comprehensive ultrastructural insights into the class-II virus fusion system function and direct mechanistic characterization of the fundamental process of protein-mediated membrane fusion.

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Mangala Prasad, V., Blijleven, J. S., Smit, J. M., Lee, K. K.. 2022-03-13. Visualization of conformational changes and membrane remodeling leading to genome delivery by viral class-II fusion machinery. https://doi.org/10.1101/2022.03.12.484076

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