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HIV-1 capsids mimic a microtubule regulator to coordinate early stages of infection.
Santos da Silva, Eveline; Shanmugapriya, Shanmugapriya; Malikov, Viacheslav; Gu, Feng; Delaney, M Keegan; Naghavi, Mojgan H.
Afiliación
  • Santos da Silva E; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Shanmugapriya S; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Malikov V; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Gu F; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Delaney MK; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Naghavi MH; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
EMBO J ; 39(20): e104870, 2020 10 15.
Article en En | MEDLINE | ID: mdl-32896909
While the microtubule end-binding protein, EB1 facilitates early stages of HIV-1 infection, how it does so remains unclear. Here, we show that beyond its effects on microtubule acetylation, EB1 also indirectly contributes to infection by delivering the plus-end tracking protein (+TIP), cytoplasmic linker protein 170 (CLIP170) to the cell periphery. CLIP170 bound to intact HIV-1 cores or in vitro assembled capsid-nucleocapsid complexes, while EB1 did not. Moreover, unlike EB1 and several other +TIPs, CLIP170 enhanced infection independently of effects on microtubule acetylation. Capsid mutants and imaging revealed that CLIP170 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 SxIP motifs found in several +TIPs, and variability across this MHR sequence correlated with the extent to which different retroviruses engage CLIP170 to facilitate infection. Our findings provide mechanistic insights into the complex roles of +TIPs in mediating early stages of retroviral infection, and reveal divergent capsid-based EB1 mimicry across retroviral species.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Infecciones por VIH / Cápside / VIH-1 / Interacciones Microbiota-Huesped / Proteínas Asociadas a Microtúbulos / Microtúbulos / Proteínas de Neoplasias Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Infecciones por VIH / Cápside / VIH-1 / Interacciones Microbiota-Huesped / Proteínas Asociadas a Microtúbulos / Microtúbulos / Proteínas de Neoplasias Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos