Site-specific Phosphorylation Differentiates Active from Inactive Forms of the Human T-cell Leukemia Virus Type 1 Tax Oncoprotein

Durkin, Sarah S.; Ward, Michael D.; Fryrear, Kimberly A.; Semmes, O. John

doi:10.1016/s0021-9258(19)84084-x

Cited by 16 publications

(1 citation statement)

References 47 publications

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“…Tax exerts its pleotropic functions through interacting with a plethora of host proteins regulated via multiple post-translational modifications [ 143 , 144 , 145 ]. The functional domains of Tax, including a nuclear localization signal (NLS) and nuclear export signal (NES), control the dynamic trafficking of Tax between the cytoplasm and nucleus for activation of NF-κB or viral gene expression [ 146 , 147 , 148 ]. However, the protein expression of Tax is almost undetectable in ATLL PBMCs, due to genetic or epigenetic changes in the viral genome; many Tax-expressing cells are also eliminated by cytotoxic T-cells (CTLs) due to the strong immunogenic properties of Tax [ 149 , 150 , 151 ].…”

Section: Innate Immune Evasion By Htlv-1mentioning

confidence: 99%

Mechanisms of Innate Immune Sensing of HTLV-1 and Viral Immune Evasion

Mohanty

Harhaj

2023

Pathogens

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Human T lymphotropic virus-1 (HTLV-1) was the first identified oncoretrovirus, which infects and establishes a persistent infection in approximately 10–20 million people worldwide. Although only ~5% of infected individuals develop pathologies such as adult T-cell leukemia/lymphoma (ATLL) or a neuroinflammatory disorder termed HTLV-1-asssociated myelopathy/tropical spastic paraparesis (HAM/TSP), asymptomatic carriers are more susceptible to opportunistic infections. Furthermore, ATLL patients are severely immunosuppressed and prone to other malignancies and other infections. The HTLV-1 replication cycle provides ligands, mainly nucleic acids (RNA, RNA/DNA intermediates, ssDNA intermediates, and dsDNA), that are sensed by different pattern recognition receptors (PRRs) to trigger immune responses. However, the mechanisms of innate immune detection and immune responses to HTLV-1 infection are not well understood. In this review, we highlight the functional roles of different immune sensors in recognizing HTLV-1 infection in multiple cell types and the antiviral roles of host restriction factors in limiting persistent infection of HTLV-1. We also provide a comprehensive overview of intricate strategies employed by HTLV-1 to subvert the host innate immune response that may contribute to the development of HTLV-1-associated diseases. A more detailed understanding of HTLV-1-host pathogen interactions may inform novel strategies for HTLV-1 antivirals, vaccines, and treatments for ATLL or HAM/TSP.

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