Gene activation therapy: from the BLV model to HAM/TSP patients.
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).
Lezin
Agnes
A
Laboratory of Virology-Immunology, Neurology and JE 2503, University Hospital of Fort-de-France, 97200 Fort-de-France, Martinique, France.
Olindo
Stephane
S
Belrose
Gildas
G
Signate
Aissatou
A
Cesaire
Raymond
R
Smadja
Didier
D
Macallan
Derek
D
Asquith
Becca
B
Bangham
Charles
C
Bouzar
Amel
A
Gillet
Nicolas
N
Defoiche
Julien
J
Florins
Arnaud
A
Verlaeten
Olivier
O
Burny
Arsene
A
Willems
Luc
L
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