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

  • Sara Rodríguez-Mora
  • Adam M. Spivak
  • Matthew A. Szaniawski
  • María Rosa López-Huertas
  • José Alcamí
  • Vicente PlanellesEmail author
  • Mayte CoirasEmail author
HIV Pathogenesis and Treatment (AL Landay and NS Utay, Section Editors)
Part of the following topical collections:
  1. Topical Collection on HIV Pathogenesis and Treatment

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.

Keywords

HIV-1 reservoir Homeostatic cytokines SAMHD1 Tyrosine kinase inhibitors Immune activation 

Notes

Funding Information

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).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sara Rodríguez-Mora
    • 1
  • Adam M. Spivak
    • 2
  • Matthew A. Szaniawski
    • 2
  • María Rosa López-Huertas
    • 3
  • José Alcamí
    • 1
    • 4
  • Vicente Planelles
    • 2
    Email author
  • Mayte Coiras
    • 1
    Email author
  1. 1.AIDS Immunopathology Unit, National Center of MicrobiologyInstituto de Salud Carlos IIIMadridSpain
  2. 2.Division of Microbiology and Immunology, Department of PathologyUniversity of Utah School of MedicineSalt Lake CityUSA
  3. 3.Infectious Diseases ServiceUniversitary Hospital Ramón y CajalMadridSpain
  4. 4.Infectious Diseases Unit, IBIDAPS, Hospital ClínicUniversity of BarcelonaBarcelonaSpain

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