The cancer-causing human retroviruses—i.e., human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2)—were both discovered in the early 1980s. About 15 million people are infected with HTLV-1 and many millions with HTLV-2 worldwide. The surprisingly recent detection of high prevalence rates among the indigenous people of central Australia has raised a new alarm and heightened attention to HTLV infection and the urgent need for increased surveillance and research.
HTLV-1 is associated with the T-lymphocytic malignancy called adult T-cell leukemia/lymphoma (ATLL) in roughly 2% of individuals infected, with another 2-3% developing a neurologic disorder called HTLV-associated myelopathy (HAM). HTLV-2 causes HAM in approximately 1-2% of infected individuals, but does not cause ATLL. HTLV-1 and HTLV-2 have served as highly informative models for the study of the epide-miology and pathogenesis of virus-associated cancers as well as autoimmune conditions such as multiple sclerosis. Two newly identified members—HTLV-3 and HTLV-4—have been discovered in bushmeat hunters from central Africa, which again emphasizes the urgent need for continuous surveillance for new human retroviruses and their capacity to cause disease.
The HTLV-1 oncoprotein is both necessary and sufficient for viral transformation, while Tax-2 - encoded by HTLV-2 - does not induce tumors in animal models. The HTLVs encode for other regulatory proteins. One protein that has received more recent attention is the HTLV-1 basic leucine zipper factor (HBZ), which inhibits Tax-mediated gene expression and is encoded as an anti-sense viral transcript. Another protein is the HTLV-1 p30II protein, which can act as an agonist of Tax-mediated transcription and serve as a multifunctional repressor of cellular gene expression.
Leukemogenesis mediated by HTLV-1 remains an important area of investigation. The focus of ongoing research remains on 1) the Tax effects on cellular transformation, 2) the consequences of perturbing cell cycle control and genome stability, 3) the role of HBZ and p30II on viral pathogenesis, 4) HTLV-1 latency and reactivation, as well as 5) therapeutic approaches. The study of HAM pathogenesis continues to hold promise as a model for neuroim-munologic diseases. New and exciting progress continues to be made in the basic understanding of viral replication of the HTLVs, particularly in virus assembly and particle structure.
The high prevalence rate of HTLV-1 infection among the indigenous population of central Australia emphasizes the important public health issues that have yet to be addressed, despite the basic epidemiology of HTLV-1 and HTLV-2 being reasonably well defined—i.e., emergence patterns in new host populations, transmission prevention, improved blood donor screening, and potential human transmission of HTLV-3 and HTLV-4.
Clinical research is particularly needed in order to potentially develop HTLV-1 and HTLV-2 vaccines, as well as development of treatment options for ATLL and HAM. This Research Topic is intended to contain both reviews and updates on research that encompass these areas.
The cancer-causing human retroviruses—i.e., human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2)—were both discovered in the early 1980s. About 15 million people are infected with HTLV-1 and many millions with HTLV-2 worldwide. The surprisingly recent detection of high prevalence rates among the indigenous people of central Australia has raised a new alarm and heightened attention to HTLV infection and the urgent need for increased surveillance and research.
HTLV-1 is associated with the T-lymphocytic malignancy called adult T-cell leukemia/lymphoma (ATLL) in roughly 2% of individuals infected, with another 2-3% developing a neurologic disorder called HTLV-associated myelopathy (HAM). HTLV-2 causes HAM in approximately 1-2% of infected individuals, but does not cause ATLL. HTLV-1 and HTLV-2 have served as highly informative models for the study of the epide-miology and pathogenesis of virus-associated cancers as well as autoimmune conditions such as multiple sclerosis. Two newly identified members—HTLV-3 and HTLV-4—have been discovered in bushmeat hunters from central Africa, which again emphasizes the urgent need for continuous surveillance for new human retroviruses and their capacity to cause disease.
The HTLV-1 oncoprotein is both necessary and sufficient for viral transformation, while Tax-2 - encoded by HTLV-2 - does not induce tumors in animal models. The HTLVs encode for other regulatory proteins. One protein that has received more recent attention is the HTLV-1 basic leucine zipper factor (HBZ), which inhibits Tax-mediated gene expression and is encoded as an anti-sense viral transcript. Another protein is the HTLV-1 p30II protein, which can act as an agonist of Tax-mediated transcription and serve as a multifunctional repressor of cellular gene expression.
Leukemogenesis mediated by HTLV-1 remains an important area of investigation. The focus of ongoing research remains on 1) the Tax effects on cellular transformation, 2) the consequences of perturbing cell cycle control and genome stability, 3) the role of HBZ and p30II on viral pathogenesis, 4) HTLV-1 latency and reactivation, as well as 5) therapeutic approaches. The study of HAM pathogenesis continues to hold promise as a model for neuroim-munologic diseases. New and exciting progress continues to be made in the basic understanding of viral replication of the HTLVs, particularly in virus assembly and particle structure.
The high prevalence rate of HTLV-1 infection among the indigenous population of central Australia emphasizes the important public health issues that have yet to be addressed, despite the basic epidemiology of HTLV-1 and HTLV-2 being reasonably well defined—i.e., emergence patterns in new host populations, transmission prevention, improved blood donor screening, and potential human transmission of HTLV-3 and HTLV-4.
Clinical research is particularly needed in order to potentially develop HTLV-1 and HTLV-2 vaccines, as well as development of treatment options for ATLL and HAM. This Research Topic is intended to contain both reviews and updates on research that encompass these areas.
