Activation of HTLV-I long terminal repeat by apoptosis inducing agents: mechanism and implications for HTLV-I pathogenicity (review).
HTLV-I is the etiological agent of adult T-cell leukemia (ATL), tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM) and certain other clinical disorders. After infection in human the virus enters into a latent state, in which very low viral gene expression can be detected. On the other hand several major characteristics of ATL and TSP/HAM indicate that their genesis requires activation of the dormant virus. TSP/HAM is characterized by high virus expression, which accounts for most of its immunopathological manifestations, whereas the process leading to ATL is believed to be initiated by the viral Tax protein, implying that it requires, at least, a temporary activation of the latent virus. Data from our and other laboratories suggest that this activation may likely be induced by environmental or/and intrinsic apoptosis-inducing factors. Moreover, we have demonstrated a mechanistic linkage between the activation of the viral promoter and the early stage of the apoptotic cascade. However, we have also shown that Tax rescues virus-expressing T-cells from apoptotic death. This suggests that Tax protein, emerging after activation of the latent virus, can rescue the host cells of the activated virus from the ultimate apoptotic death. Since the development of both TSP/HAM and ATL seems to depend on the viral Tax protein, we describe a possible system for anti Tax gene-therapy approach based on a negative transdominant mutant Tax gene.
Schavinsky-Khrapunsky
Yana
Y
Department of Microbiology and Immunology, Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Gold
Evgenia
E
Ben-Aroya
Zahi
Z
Torgeman
Amram
A
Aboud
Mordechai
M
Huleihel
Mahmoud
M
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000473:pathology / Q000821:virology*; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D020079:Terminal Repeat Sequences / Q000235:genetics*; D014775:Virus Activation
D000998:Antiviral Agents