Structural and functional analysis of natural capsid variants suggests sialic acid-independent entry of BK polyomavirus

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Sorin, Marie, N | Di Maio, Antonio | Silva, Lisete, M | Ebert, Domenic | Delannoy, Clément, P | Nguyen, Ngoc-Khanh | Guerardel, Yann | Chai, Wengang | Halary, Franck | Renaudin-Autain, Karine | Liu, Yan | Bressollette-Bodin, Céline | Stehle, Thilo | Mcilroy, Dorian

Edité par CCSD ; Elsevier Inc -

International audience. BK polyomavirus (BKPyV) is an opportunistic pathogen that uses the b-series gangliosides GD1b and GT1bas entry receptors. Here, we characterize the impact of naturally occurring VP1 mutations on gangliosidebinding, VP1 protein structure, and virus tropism. Infectious entry of single mutants E73Q and E73A andthe triple mutant A72V-E73Q-E82Q (VQQ) remains sialic acid dependent, and all three variants acquire bindingto a-series gangliosides, including GD1a. However, the E73A and VQQ variants lose the ability to infectganglioside-complemented cells, and this correlates with a clear shift of the BC2 loop in the crystal structuresof E73A and VQQ. On the other hand, the K69N mutation in the K69N-E82Q variant leads to a steric clash thatprecludes sialic acid binding. Nevertheless, this mutant retains significant infectivity in 293TT cells, which isnot dependent on heparan sulfate proteoglycans, implying that an unknown sialic acid-independent entry receptorfor BKPyV exists.

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