HTLV‐1 persistent infection and ATLL oncogenesis

Abstract

Human T‐cell leukemia virus type 1 (HTLV‐1) is an oncogenic retrovirus; whereas HTLV‐1 mainly persists in the infected host cell as a provirus, it also causes a malignancy called adult T‐cell leukemia/lymphoma (ATLL) in about 5% of infection. HTLV‐1 replication is in most cases silent in vivo and viral de novo infection rarely occurs; HTLV‐1 rather relies on clonal proliferation of infected T cells for viral propagation as it multiplies the number of the provirus copies. It is mechanistically elusive how leukemic clones emerge during the course of HTLV‐1 infection in vivo and eventually cause the onset of ATLL. This review summarizes our current understanding of HTLV‐1 persistence and oncogenesis, with the incorporation of recent cutting‐edge discoveries obtained by high‐throughput sequencing.

Clinical and Mechanistic Implications of R-Loops in Human Leukemias

“…Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus of the human T-lymphotropic virus (HTLV) family, which induces very aggressive adult T-cell leukemia/lymphoma (ATL) [ 94 , 95 , 96 ]. HTLV-1 is also associated with myelopathy, uveitis, Strongyloides stercoralis hyperinfection, and other diseases.…”

Oncogenic viruses and host lipid metabolism: a new perspective

“…Tax-1 is mainly involved in the initiation of neoplastic transformation and the host inflammatory response, but its expression may be lost during both cell clonal proliferation and tumorigenesis. In contrast, HBZ is consistently expressed in all patients with ATLL, and plays a role in the proliferation and maintenance of leukemic cells [171].…”

Disseminated itching papules in a Jamaican patient

“…Key roles are attributed to the viral oncogene transactivator protein (Tax) and the HTLV‐1 basic leucine zipper factor (HBZ). Tax can activate signaling pathways of T‐cell activation and expansion, whereas HBZ plays an important role in HTLV‐1 survival in infected cells 6 . The sometimes severe hypercalcemia is due to cytokines released from the malignant cells, which lead to increased expression of parathyroid hormone‐related protein, tumor necrosis factor‐beta, interleukin 1, and RANKL (receptor activator of nuclear factor‐κB ligand), 7 causing bone resorption and thereby osteolysis and serum hypercalcemia.…”