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bioRxiv · 10.1101/2021.02.08.430194

The envelope cytoplasmic tail regulates HIV-1 assembly and spread

Snetkov, X.·Haider, T.·Mesner, D.·Groves, N.·Van Engeleburg, S.·Jolly, C.
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Abstract

The HIV-1 envelope (Env) is an essential determinant of viral infectivity, tropism and spread between T cells. Lentiviral Env contain an unusually long 150 amino acid cytoplasmic tail (EnvCT) but the function of the EnvCT and conserved domains within it remain largely uncharacterised. Here we identified a highly conserved tryptophan motif at position 757 (W757) in the LLP-2 alpha helix of the EnvCT as a key determinant for HIV-1 replication and spread between T cells. Strikingly we find that mutating W757 had wide-ranging consequences including altering Env mobility in the plasma membrane, preventing Env and Gag recruitment to sites of cell-cell contact for virological synapse (VS) formation and cell-cell spread, and impeding viral fusion. Notably, W757 was also required for efficient virus budding, revealing a previously unappreciated role for the EnvCT in regulating HIV-1 assembly and egress. We conclude that W757 is a key residue that stabilises the structural integrity and function of Env, consistent with the recent model that this region of the EnvCT acts as a critical supporting baseplate for Env.

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Snetkov, X., Haider, T., Mesner, D., Groves, N., Van Engeleburg, S., Jolly, C.. 2021-02-08. The envelope cytoplasmic tail regulates HIV-1 assembly and spread. https://doi.org/10.1101/2021.02.08.430194

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