Tyrosine Kinase Inhibition: a New Perspective in the Fight against HIV
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.
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.
TKIs together with cART will interfere with HIV-1 latent reservoir persistence, favoring the prospect for viral eradication.
KeywordsHIV-1 reservoir Homeostatic cytokines SAMHD1 Tyrosine kinase inhibitors Immune activation
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.
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