HIV-1 binds dynein directly to hijack microtubule transport machinery

Badieyan, S.; Lichon, D.; Andreas, M. P.; Gillies, J. P.; Peng, W.; Shi, J.; DeSantis, M. E.; Aiken, C. R.; Böcking, T.; Giessen, T. W.; Campbell, E. M.; Cianfrocco, M. A.

doi:10.1101/2023.08.29.555335

bioRxiv · 10.1101/2023.08.29.555335

HIV-1 binds dynein directly to hijack microtubule transport machinery

Badieyan, S.·Lichon, D.·Andreas, M. P.·Gillies, J. P.·Peng, W.·Shi, J.·DeSantis, M. E.·Aiken, C. R.·Böcking, T.·Giessen, T. W.·Campbell, E. M.·Cianfrocco, M. A.

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Abstract

Viruses exploit host cytoskeletal elements and motor proteins for trafficking through the dense cytoplasm. Yet the molecular mechanism that describes how viruses connect to the motor machinery is unknown. Here, we demonstrate the first example of viral microtubule trafficking from purified components: HIV-1 hijacking microtubule transport machinery. We discover that HIV-1 directly binds to the retrograde microtubule-associated motor, dynein, and not via a cargo adaptor, as previously suggested. Moreover, we show that HIV-1 motility is supported by multiple, diverse dynein cargo adaptors as HIV-1 binds to dynein light and intermediate chains on dyneins tail. Further, we demonstrate that multiple dynein motors tethered to rigid cargoes, like HIV-1 capsids, display reduced motility, distinct from the behavior of multiple motors on membranous cargoes. Our results introduce a new model of viral trafficking wherein a pathogen opportunistically hijacks the microtubule transport machinery for motility, enabling multiple transport pathways through the host cytoplasm.

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Badieyan, S., Lichon, D., Andreas, M. P., Gillies, J. P., Peng, W., Shi, J., DeSantis, M. E., Aiken, C. R., Böcking, T., Giessen, T. W., Campbell, E. M., Cianfrocco, M. A.. 2023-08-29. HIV-1 binds dynein directly to hijack microtubule transport machinery. https://doi.org/10.1101/2023.08.29.555335

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