HTLV-1 is a retrovirus that infects T-cells and can cause adult T-cell leukemia/lymphoma (ATLL). It is endemic in parts of Japan, the Caribbean, South America, and Africa. Worldwide, 15 to 20 million people are infected. HTLV-1 is transmitted sexually, through blood products, or breastfeeding. Only 3-5% of those infected develop leukemia, typically after a long latent period of 40-60 years. The virus has tropism for CD4+ T-cells and the TAX and HBZ viral proteins interact with host cell genes and pathways to stimulate proliferation and inhibit tumor suppression, eventually leading to monoclonal proliferation and leukemia.

1. Human T-Cell Leukemia Virus
Type 1 (HTLV-1)

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.