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

Overview

Journal Curr HIV/AIDS Rep

Publisher Current Science

Specialty Infectious Diseases

Date 2019 Sep 12

PMID 31506864

Citations 7

Authors

Sara Rodriguez-Mora

Adam M Spivak

Matthew A Szaniawski

Maria Rosa Lopez-Huertas

Jose Alcami

Vicente Planelles

Mayte Coiras

Affiliations

Soon will be listed here.

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

Citing Articles

Sustained antiviral response against HIV-1 infection in peripheral blood mononuclear cells from people with chronic myeloid leukemia treated with ponatinib.

Manzanares M, Ramos-Martin F, Rodriguez-Mora S, Casado-Fernandez G, Sanchez-Menendez C, Simon-Rueda A Front Pharmacol. 2024; 15:1426974.

PMID: 39380908 PMC: 11460598. DOI: 10.3389/fphar.2024.1426974.

Targeting Viral Transcription for HIV Cure Strategies.

Izquierdo-Pujol J, Puertas M, Martinez-Picado J, Moron-Lopez S Microorganisms. 2024; 12(4).

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The role of TEMRA cell-mediated immune senescence in the development and treatment of HIV disease.

Guo L, Liu X, Su X Front Immunol. 2023; 14:1284293.

PMID: 37901239 PMC: 10602809. DOI: 10.3389/fimmu.2023.1284293.

Past and future of HIV infection. A document based on expert opinion.

Bouza E, Arribas J, Alejos B, Bernardino J, Coiras M, Coll P Rev Esp Quimioter. 2022; 35(2):131-156.

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Co-receptor signaling in the pathogenesis of neuroHIV.

Nickoloff-Bybel E, Festa L, Meucci O, Gaskill P Retrovirology. 2021; 18(1):24.

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