Special Issue "Recent Developments in HTLV Research"
Deadline for manuscript submissions: closed (31 March 2011).
Human T-lymphotropic retrovirus types 1 and 2 (HTLV-1 and HTLV-2) were discovered in the early 1980’s. These viruses are now estimated to infect up to 14 million (HTLV-1) and several million (HTLV-2) people worldwide. HTLV-1 causes a T-lymphocytic malignancy known as adult T-cell leukemia/lymphoma (ATLL) in about 2 percent of those infected, and a neurologic disorder called HTLV-associated myelopathy (HAM) in another 2 to 3 percent. HTLV-2 does not cause ATLL, but does cause HAM in 1 to 2 percent of infected individuals. These viruses serve as excellent models for the epidemiology and pathogenesis of viral-associated cancers, other human retroviral infections, and autoimmune conditions such as multiple sclerosis. The recent discovery of two new members of the HTLV family, HTLV-3 and HTLV-4 in Central African bushmeat hunters emphasizes the need for continued surveillance for new human retroviruses and analysis of these new viruses for disease-causing potential. HTLV-1 encodes a viral oncoprotein, Tax-1, which is necessary and sufficient for viral transformation while the HTLV-2 Tax-2 protein does not cause tumors in animal models. Other regulatory proteins encoded by HTLVs include the HTLV-1 basic leucine zipper factor (HBZ), which is encoded on an anti-sense viral transcript and inhibits Tax mediated viral gene expression. The HTLV-1 p30II protein is also an agonist for Tax-mediated transcription and is a multifunctional repressor of cellular gene expression.
HTLV-1 mediated leukemogenesis is a topic of intense investigation. Current research efforts are focused on the effects of Tax on cellular transcription and consequent perturbations of genome stability and cell cycle control, role of regulatory proteins
such as HBZ and p30II in HTLV pathogenesis, mechanisms of viral entry, and development of therapeutic approaches. Research into the pathogenesis of HAM will provide important insights into this disease as well as a model for other neuroimmunologic diseases. Although the basic epidemiology of HTLV-1 and -2 has been reasonably well defined, important public health issues remain to be addressed, including patterns of emergence into new host populations, prevention of transmission, improved confirmatory tests for blood donor screening, and the potential for HTLV-3 and HTLV-4 to be transmitted from person-to-person and to cause human disease. Ongoing clinical research is needed to develop potential HTLV-I and –II vaccines, and treatments for ATL and HAM. This special issue will contain reviews and updates on recent advances in research focused on each of these areas.
- human T cell leukemia virus
- adult T cell leukemia
- HTLV-associated myelopathy
- accessory proteins p30, p12, p13
- new HTLV viruses
- transcription control
- cell cycle/senescence
- genome instability
- clinical trials
- animal models
- viral entry