HTLV-1 and apoptosis: role in cellular transformation and recent advances in therapeutic approaches.
A universal cellular defense mechanism against viral invasion is the elimination of infected cells through apoptotic cell death. To counteract host defenses many viruses have evolved complex apoptosis evasion strategies. The oncogenic human retrovirus HTLV-1 is the etiological agent of adult-T-cell leukemia/lymphoma (ATLL) and the neurodegenerative disease known as HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The poor prognosis in HTLV-1-induced ATLL is linked to the resistance of neoplastic T cells against conventional therapies and the immuno-compromised state of patients. Nevertheless, several studies have shown that the apoptotic pathway is largely intact and can be reactivated in ATLL tumor cells to induce specific killing. A better understanding of the molecular mechanisms employed by HTLV-1 to counteract cellular death pathways remains an important challenge for future therapies and the treatment of HTLV-1-associated diseases.
Taylor
John M
JM
Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, 3025 Wahl Hall West, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
Nicot
Christophe
C
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002472:Cell Transformation, Viral / Q000502:physiology*; D016356:Gene Products, tax / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology; D053612:Janus Kinases / Q000502:physiology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000821:virology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy / Q000821:virology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000502:physiology; D012191:Retroviridae Proteins / Q000502:physiology; D050791:STAT Transcription Factors / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology
D016356:Gene Products, tax; D016328:NF-kappa B; D015375:Receptors, Interleukin-2; D012191:Retroviridae Proteins; D050791:STAT Transcription Factors; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C084305:p12I protein, Human T-lymphotropic virus 1; C072813:rof protein, Human T-lymphotropic virus 1; C072814:tof protein, Human T-lymphotropic virus 1; D014212:Tretinoin; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase