Gene activation therapy: from the BLV model to HAM/TSP patients.

in Frontiers in bioscience (scholar edition) (2009), 1

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 ... [more ▼]

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). [less ▲]

Valproate synergizes with purine nucleoside analogues to induce apoptosis of B-chronic lymphocytic leukaemia cells.

in British journal of haematology (2009), 144(1),

Reduced levels of reactive oxygen species correlate with inhibition of apoptosis, rise in thioredoxin expression and increased bovine leukemia virus proviral loads.

in Retrovirology (2009), 6

BACKGROUND: Bovine Leukemia virus (BLV) is a deltaretrovirus that induces lymphoproliferation and leukemia in ruminants. In ex vivo cultures of B lymphocytes isolated from BLV-infected sheep show that ... [more ▼]

BACKGROUND: Bovine Leukemia virus (BLV) is a deltaretrovirus that induces lymphoproliferation and leukemia in ruminants. In ex vivo cultures of B lymphocytes isolated from BLV-infected sheep show that spontaneous apoptosis is reduced. Here, we investigated the involvement of reactive oxygen species (ROS) in this process. RESULTS: We demonstrate that (i) the levels of ROS and a major product of oxidative stress (8-OHdG) are reduced, while the thioredoxin antioxidant protein is highly expressed in BLV-infected B lymphocytes, (ii) induction of ROS by valproate (VPA) is pro-apoptotic, (iii) inversely, the scavenging of ROS with N-acetylcysteine inhibits apoptosis, and finally (iv) the levels of ROS inversely correlate with the proviral loads. CONCLUSION: Together, these observations underline the importance of ROS in the mechanisms of inhibition of apoptosis linked to BLV infection. [less ▲]

How HTLV-1 may subvert miRNAs for persistence and transformation.

in Retrovirology (2008), 5

Distinct mechanisms are used by viruses to interact with cellular miRNAs. The role of microRNAs in viral replication and persistence ranges from viral-encoded microRNAs to suppressors of RNA interference ... [more ▼]

Distinct mechanisms are used by viruses to interact with cellular miRNAs. The role of microRNAs in viral replication and persistence ranges from viral-encoded microRNAs to suppressors of RNA interference. Viruses can also exploit cellular miRNAs for influencing cellular metabolism to ensure efficient replication or latency. In particular, two recent studies provide examples of how HTLV-1 may co-opt or subvert cellular miRNAs for persistent replication and oncogenic purposes. The pathways modulated by these described miRNAs are critically involved in apoptosis, proliferation and innate immune response. [less ▲]

Detection of viral genomes of caprine arthritis-encephalitis virus (CAEV) in semen and in genital tract tissues of male goat

in Theriogenology (2008)

Dynamique cellulaire de la pathogenèse induite par le virus de la leucémie bovine

in Virologie (2007)

The called "Tat" of small ruminant lentivirus is a Vpr like protein

in Current Topics in Virology (2004)

CAPRINE ARTHRITIS ENCEPHALITIS VIRUS (CAEV) EXPRESSING THE SIV VPR/VPX GENES INDUCES PROPERTIES SIMILAR TO ANTI-CANCER DRUGS

in Bulletin of the Veterinary Institute in Pulawy =Biuletyn Instytutu Weterynarii w Puławach (2003)

Lack of trans-activation function for Maedi Visna virus and Caprine arthritis encephalitis virus Tat proteins

in Virology (2003)

Clearance of a productive lentivirus infection in calves experimentally inoculated with caprine arthritis-encephalitis virus

in Journal of Virology (2003)