Human T-Cell Leukemia Virus Type 1 Envelope Protein: Post-Entry Roles in Viral Pathogenesis

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and fatal CD4+ T-cell malignancy, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neurological disease. Disease progression in infected individuals is the result of HTLV-1-driven clonal expansion of CD4+ T-cells and is generally associated with the activities of the viral oncoproteins Tax and Hbz. A closely related virus, HTLV-2, exhibits similar genomic features and the capacity to transform T-cells, but is non-pathogenic. In vitro, HTLV-1 primarily immortalizes or transforms CD4+ T-cells, while HTLV-2 displays a transformation tropism for CD8+ T-cells. This distinct tropism is recapitulated in infected people. Through comparative studies, the genetic determinant for this divergent tropism of HTLV-1/2 has been mapped to the viral envelope (Env). In this review, we explore the emerging roles for Env beyond initial viral entry and examine current perspectives on its contributions to HTLV-1-mediated disease development.

Emerging Roles of B56 Phosphorylation and Binding Motif in PP2A-B56 Holoenzyme Biological Function

“…An additional illustration of viral B56 recruitment through the LxxIxE SLiM was observed in the Human T-cell lymphotropic virus type 1 (HTLV-1). HTLV-1 is a deltaretrovirus that is one of the most oncogenic human viruses in existence [ 56 ]. Integrase (IN) is responsible for facilitating the integration of viral genetic material into the host genome, a crucial step in the replication cycle of deltaretroviruses.…”

Immune landscape of viral cancers: Insights from single‐cell sequencing

“…17 HTLV-1 causes approximately 5−20 million infections worldwide, with only 5% of cases developing ATL. 17 HTLV-1 gene products Tax and Hbz are key drivers of cellular transformation and T-cell proliferation which mediate leukemogenesis, 18 although the viral envelope may also play a pathogenic role in HTLV-1-induced oncogenesis. 18 However, the mechanism underlying malignant transformation of infected cells and dynamic alteration of the TIME in ATL patients is still relatively unclear.…”