Sara Rodríguez-Mora1, Adam M Spivak2, Matthew A Szaniawski2, María Rosa López-Huertas3, José Alcamí1,4, Vicente Planelles5, Mayte Coiras6. 1. AIDS Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo km2, 28220, Madrid, Spain. 2. Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA. 3. Infectious Diseases Service, Universitary Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km. 9, 100, 28034, Madrid, Spain. 4. Infectious Diseases Unit, IBIDAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain. 5. Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA. vicente.planelles@path.utah.edu. 6. AIDS Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo km2, 28220, Madrid, Spain. mcoiras@isciii.es.
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.
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, dasatinibblocks 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.
Authors: Deanna Saylor; Alex M Dickens; Ned Sacktor; Norman Haughey; Barbara Slusher; Mikhail Pletnikov; Joseph L Mankowski; Amanda Brown; David J Volsky; Justin C McArthur Journal: Nat Rev Neurol Date: 2016-03-11 Impact factor: 42.937
Authors: E Bouza; J R Arribas; B Alejos; J I Bernardino; M Coiras; P Coll; J Del Romero; M J Fuster; M Górgolas; A Gutiérrez; D Gracia; V Hernando; J Martínez-Picado; J M Martínez Sesmero; E Martínez; S Moreno; B Mothe; M L Navarro; D Podzamczer; F Pulido; J T Ramos; E Ruiz-Mateos; I Suárez García; E Palomo Journal: Rev Esp Quimioter Date: 2022-01-12 Impact factor: 1.553
Authors: Lorena Vigón; Paula Martínez-Román; Sara Rodríguez-Mora; Montserrat Torres; María C Puertas; Elena Mateos; María Salgado; Antonio Navarro; Matilde Sánchez-Conde; Juan Ambrosioni; Miguel Cervero; Christoph Wyen; Christian Hoffmann; José M Miró; José Alcamí; Daniel Podzamczer; Valentín García-Gutiérrez; Javier Martínez-Picado; Verónica Briz; María Rosa López-Huertas; Vicente Planelles; Mayte Coiras Journal: Biochem Pharmacol Date: 2021-06-26 Impact factor: 6.100