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 2. INTRODUCTION The deltaretrovirus genus comprises a series of related viruses infecting lymphocytes of human, primates and ruminants (1). The prototypes of this genus are HTLV- 1 (human T-lymphotropic virus type 1) and BLV (bovine leukemia virus). These two viruses share a series structural and functional properties but also harbor unique characteristics (Table 1). 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 ΗTLV-1 induced myelopathy / tropical spastic paraparesis (HAM/TSP). 205