2. Human T-Cell Leukemia Virus Type 1
(HTLV-1)
Epidemiology
First retrovirus involved in human cancer.
HTLV-1 causes adult T-cell leukemia/lymphoma(ATLL), a tumour that is endemic in
- Certain parts of Japan
The Caribbean basin
South America and Africa
And found sporadically elsewhere, including the United States.
Worldwide, 15 to 20 million people are infected with HTLV-1.
3. Mode of transmission
Human infection requires transmission of infected T cells via
• Sexual intercourse
• Blood products
• Breastfeeding.
Leukemia develops in only 3% to 5% of the infected individuals, typically after a
long latent period of 40 to 60 years.
4. HTLV-1 ONCOGENEIS
The molecular mechanism of ATLL leukaemogenesis by HTLV-1 infection of CD4+ T
lymphocytes is not clear.
Similar to human immunodeficiency virus (HIV), which causes AIDS, HTLV-1 has
tropism for CD4+ T cells, and hence this subset of T cells is the major target for
neoplastic transformation.
Oncoproteins :
1. TAX - regulates the expression of cellular genes controlling T- cell
replication
2. HBZ (HTLV 1 Basic leucine Zipper factor) – is a transcription factor
5. Oncogenesis process is multifactorial :
TAX viral protein interacts with transcription factor, NF- kB
stimulates genes for cytokines (interleukins) and their receptors in
infected T- cells
which activates proliferation of T-cells by autocrine pathway.
And also inappropriate gene expression activates pathway of the cell
proliferation by :
1. activation of cyclins
2. inactivation of tumour-suppressor genes CDKN2A/p16
and TP53
stimulating cell cycle.
Initially, proliferation of infected T-cells is polyclonal but subsequently
several mutations appear due to TAX-based genomic changes in the host
cell and monoclonal proliferation of leukaemia occurs.
