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HIV ‐1 capsids mimic a microtubule regulator to coordinate early stages of infection
Author(s) -
Santos da Silva Eveline,
Shanmugapriya Shanmugapriya,
Malikov Viacheslav,
Gu Feng,
Delaney M Keegan,
Naghavi Mojgan H
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020104870
Subject(s) - capsid , biology , microtubule , plasma protein binding , microbiology and biotechnology , virology , virus
While the microtubule end‐binding protein, EB 1 facilitates early stages of HIV ‐1 infection, how it does so remains unclear. Here, we show that beyond its effects on microtubule acetylation, EB 1 also indirectly contributes to infection by delivering the plus‐end tracking protein (+ TIP ), cytoplasmic linker protein 170 ( CLIP 170) to the cell periphery. CLIP 170 bound to intact HIV ‐1 cores or in vitro assembled capsid–nucleocapsid complexes, while EB 1 did not. Moreover, unlike EB 1 and several other + TIP s, CLIP 170 enhanced infection independently of effects on microtubule acetylation. Capsid mutants and imaging revealed that CLIP 170 bound HIV ‐1 cores in a manner distinct from currently known capsid cofactors, influenced by pentamer composition or curvature. Structural analyses revealed an EB ‐like + TIP ‐binding motif within the capsid major homology region ( MHR ) that binds Sx IP motifs found in several + TIP s, and variability across this MHR sequence correlated with the extent to which different retroviruses engage CLIP 170 to facilitate infection. Our findings provide mechanistic insights into the complex roles of + TIP s in mediating early stages of retroviral infection, and reveal divergent capsid‐based EB 1 mimicry across retroviral species.