title: Gene activation therapy: from the BLV model to HAM/TSP patients.
abstract: HTLV-1 (human T-lymphotropic virus type 1) and BLV (bovine leukemia virus) are two related retroviruses infecting CD4+ and B lymphocytes in humans and ruminants, respectively. During infection, the host-pathogen interplay is characterized by very dynamic kinetics resulting in equilibrium between the virus, which attempts to proliferate, and the immune response, which seeks to exert tight control of the virus. A major determinant of disease induction by both viruses is the accumulation of provirus in peripheral blood. In the absence of viral proteins, virus infected cells escape recognition and destruction by the host immune response. We propose a novel therapeutic strategy based on transient activation of viral expression using epigenetic modulators; this exposes infected cells to the immune response and results in significant reductions in proviral loads. In the absence of satisfactory therapies, this viral gene-activation strategy might delay progression, or even be curative, for HTLV-1 induced myelopathy / tropical spastic paraparesis (HAM/TSP).
authors.affiliation: Laboratory of Virology-Immunology, Neurology and JE 2503, University Hospital of Fort-de-France, 97200 Fort-de-France, Martinique, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Lezin
authors.forename: Stephane
authors.initials: S
authors.lastname: Olindo
authors.forename: Gildas
authors.initials: G
authors.lastname: Belrose
authors.forename: Aissatou
authors.initials: A
authors.lastname: Signate
authors.forename: Raymond
authors.initials: R
authors.lastname: Cesaire
authors.forename: Didier
authors.initials: D
authors.lastname: Smadja
authors.forename: Derek
authors.initials: D
authors.lastname: Macallan
authors.forename: Becca
authors.initials: B
authors.lastname: Asquith
authors.forename: Charles
authors.initials: C
authors.lastname: Bangham
authors.forename: Amel
authors.initials: A
authors.lastname: Bouzar
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gillet
authors.forename: Julien
authors.initials: J
authors.lastname: Defoiche
authors.forename: Arnaud
authors.initials: A
authors.lastname: Florins
authors.forename: Olivier
authors.initials: O
authors.lastname: Verlaeten
authors.forename: Arsene
authors.initials: A
authors.lastname: Burny
authors.forename: Luc
authors.initials: L
authors.lastname: Willems
mesh_terms: D000818:Animals; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D001909:Leukemia Virus, Bovine / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D015493:Paraparesis, Tropical Spastic / Q000235:genetics / Q000628:therapy*; D012756:Sheep