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Tyrosine Kinase Inhibition: a New Perspective in the Fight against HIV

  • HIV Pathogenesis and Treatment (AL Landay and NS Utay, Section Editors)
  • Published:
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Abstract

Purpose of Review

HIV-1 infection is incurable due to the existence of latent reservoirs that persist in the face of cART. In this review, we describe the existence of multiple HIV-1 reservoirs, the mechanisms that support their persistence, and the potential use of tyrosine kinase inhibitors (TKIs) to block several pathogenic processes secondary to HIV-1 infection.

Recent Findings

Dasatinib interferes in vitro with HIV-1 persistence by two independent mechanisms. First, dasatinib blocks infection and potential expansion of the latent reservoir by interfering with the inactivating phosphorylation of SAMHD1. Secondly, dasatinib inhibits the homeostatic proliferation induced by γc-cytokines. Since homeostatic proliferation is thought to be the main mechanism behind the maintenance of the latent reservoir, we propose that blocking this process will gradually reduce the size of the reservoir.

Summary

TKIs together with cART will interfere with HIV-1 latent reservoir persistence, favoring the prospect for viral eradication.

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Funding

This work was supported by NIH UM1-AI126620 (BEAT-HIV Delaney Collaboratory, co-funded by NIAID, NIMH, NINDS, and NIDA); NIH grant R01AI143567; the Spanish Ministry of Economy and Competitiveness (SAF2013-44677-R, SAF2016-78480-R); the Spanish Ministry of Science, Innovation and Universities (FIS PI16CIII/00034-ISCIII- FEDER); and Spanish AIDS Research Network RD16CIII/0002/0001 that is included in the Spanish I+D+I Plan and is co-financed by ISCIII-Subdirección General de Evaluación and European Funding for Regional Development (FEDER).

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Authors and Affiliations

  1. AIDS Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo km2, 28220, Madrid, Spain

    Sara Rodríguez-Mora, José Alcamí & Mayte Coiras

  2. Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA

    Adam M. Spivak, Matthew A. Szaniawski & Vicente Planelles

  3. Infectious Diseases Service, Universitary Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km. 9, 100, 28034, Madrid, Spain

    María Rosa López-Huertas

  4. Infectious Diseases Unit, IBIDAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain

    José Alcamí

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  1. Sara Rodríguez-Mora
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  2. Adam M. Spivak
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  3. Matthew A. Szaniawski
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  4. María Rosa López-Huertas
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  5. José Alcamí
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  6. Vicente Planelles
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  7. Mayte Coiras
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Correspondence to Vicente Planelles or Mayte Coiras.

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Rodríguez-Mora, S., Spivak, A.M., Szaniawski, M.A. et al. Tyrosine Kinase Inhibition: a New Perspective in the Fight against HIV. Curr HIV/AIDS Rep 16, 414–422 (2019). https://doi.org/10.1007/s11904-019-00462-5

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