HTLV1 retrovirus
Human T lymphotropic virus type 1 (HTLV1) was the first human retrovirus to be discovered and is endemic in certain areas (especially SW Japan, the Caribbean and parts of Africa and South America) where up to 10% or more of the population may be infected1 (Figure 2.1).
The virus naturally infects CD4+ T lymphocytes and can be transmitted between close contacts through blood transfer or from mother to infant through cells in breast milk. In most cases the infection is harmless. However, as many as 1 in 20 infected individuals eventually develop a type of adult T cell leukaemia in which every tumour cell carries a clonally integrated HTLV1 provirus2, 3.
HTLV1 differs from the standard 'chronically oncogenic' and 'acutely oncogenic' retroviruses in its mechanism of action; it appears to drive cell growth through expression of a particular viral protein, Tax, in latently-infected cells (Figure 2.2).
Tax can transactivate expression of a number of key cellular genes that enhance cell growth. The best examples are the genes encoding interleukin 2 (a T cell growth factor) and the interleukin 2 receptor (a molecule that allows cells to respond to the growth factor). As a consequence, the infected cells not only make their own growth signals, but also respond to them4.
HTLV1 induces a rather weak growth transformation of T cells in the laboratory but, in the body, is probably never sufficiently strong to induce T cell leukaemia on its own. However, a virally infected cell in which growth controls have even partly broken down, is more susceptible to further genetic accidents.During persistent infection a gradual build-up of HTLV1-positive T cells which have accumulated additional genetic changes may occur. Eventually this can lead to selection and outgrowth of a fully malignant, HTLV1-positive clone (Figure 2.2). At this stage malignant cell growth can occur i the absence of tax gene expression.
References for HTLV virus and cancer
- Proietti, F.A., et al., Global epidemiology of HTLV-I infection and associated diseases. Oncogene, 2005. 24(39): p. 6058-68.
- Yoshida, M., Discovery of HTLV-1, the first human ertrovirus, its unique regulatory mechanisms, and insights into pathogenesis. Oncogene, 2005. 24(39): p. 5931-5937.
- IARC, Human Immunodeficiency Viruses Summary of the reported data and evaluation. 1996. p.
- Grassmann, R., M. ABoud, and K. Jeang, Molecular mechanisms of cellular transformation by HTLV-1 Tax. Oncogene, 2005. 24(39): p. 5976-5985.
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