<scp>IFI</scp>16 regulates <scp>HTLV</scp>‐1 replication through promoting <scp>HTLV</scp>‐1 <scp>RTI</scp>‐induced innate immune responses

Yang, Bo; Song, Di; Liu, Yue; Cui, Yuhan; Lu, Guangjian; Di, Wenyu; Xing, Hongxia; Ma, Lingling; Guo, Zhixin; Guan, Yuhe; Wang, Hui; Wang, Jie

doi:10.1002/1873-3468.13077

Cited by 11 publications

(5 citation statements)

References 34 publications

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“…If HTLV-1 infection can impact IFN-I production and signaling, this virus can also be recognized by several sensors, such as STING (Stimulator of Interferon Genes), IFI16 (Interferon-γ Inducible protein 16), and Ku70 [88,89,90], in the infected cells and by TLR-7 in plasmacytoid dendritic cells [91], which leads to the induction of IFN-I production, thus, potentially contributing to the HTLV-1 infection control. However, it is worth noting that the ATLL and HAM/TSP patients present a depletion of plasmacytoid dendritic cells [92,93,94], further supporting the role of IFN-I in the control of the HTLV-1 infection.…”

Section: Paradoxical Functions Of the Ifn-i Antiviral Cytokinementioning

confidence: 99%

Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

Futsch

Prates

Mahieux

et al. 2018

Viruses

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Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of a neural chronic inflammation, called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and of a malignant lymphoproliferation, called the adult T-cell leukemia/lymphoma (ATLL). The mechanisms through which the HTLV-1 induces these diseases are still unclear, but they might rely on immune alterations. HAM/TSP is associated with an impaired production of pro-inflammatory cytokines and chemokines, such as IFN-γ, TNF-α, CXCL9, or CXCL10. ATLL is associated with high levels of IL-10 and TGF-β. These immunosuppressive cytokines could promote a protumoral micro-environment. Moreover, HTLV-1 infection impairs the IFN-I production and signaling, and favors the IL-2, IL-4, and IL-6 expression. This contributes both to immune escape and to infected cells proliferation. Here, we review the landscape of cytokine dysregulations induced by HTLV-1 infection and the role of these cytokines in the HTLV-1-associated diseases progression.

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Section: Paradoxical Functions Of the Ifn-i Antiviral Cytokinementioning

confidence: 99%

Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

Futsch

Prates

Mahieux

et al. 2018

Viruses

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“…Human embryonic kidney cell line (HEK293T) and a human cervical cancer cell line (HeLa) were obtained from American Type Culture Collection (Manassas, VA, USA) and maintained in Dulbecco’s modified Eagle’s medium (Gibco, Grand Island, NY, USA), supplemented with 10% fetal bovine serum (FBS) (Gibco) and 1% penicillin-streptomycin. HTLV-1–transformed cell lines MT2 and MT4 were described previously ( 42 ). Jurkat, MT2, and MT4 cells were grown in RPMI 1640 medium containing 1% penicillin-streptomycin and supplemented with 10% FBS.…”

Section: Methodsmentioning

confidence: 99%

PCBP1 interacts with the HTLV-1 Tax oncoprotein to potentiate NF-κB activation

Su,

Kang,

Niu

et al. 2024

Front. Immunol.

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Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma. The HTLV-1 Tax constitutively activates nuclear factor-κB (NF-κB) to promote the survival and transformation of HTLV-1-infected T cells. Despite extensive study of Tax, how Tax interacts with host factors to regulate NF-κB activation and HTLV-1–driven cell proliferation is not entirely clear. Here, we showed that overexpression of Poly (rC)–binding protein 1 (PCBP1) promoted Tax-mediated IκB kinase (IKK)–NF-κB signaling activation, whereas knockdown of PCBP1 attenuated Tax-dependent IKK–NF-κB activation. However, Tax activation of HTLV-1 long terminal repeat was unaffected by PCBP1. Furthermore, depletion of PCBP1 led to apoptosis and reduced proliferation of HTLV-1–transformed cells. Mechanistically, PCBP1 interacted and co-localized with Tax in the cytoplasm, and PCBP1 KH3 domain was indispensable for the interaction between PCBP1 and Tax. Moreover, PCBP1 facilitated the assembly of Tax/IKK complex. Collectively, our results demonstrated that PCBP1 may exert an essential effect in Tax/IKK complex combination and subsequent NF-κB activation, which provides a novel insight into the pathogenetic mechanisms of HTLV-1.

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“…IFI16 forms a scaffold with viral DNA to recruit the endoplasmic reticulum (ER) adaptor STING and TANK-binding kinase 1 (TBK1) for the activation of IRF3 and NF-κB signaling to induce IFN-β and initiate antiviral activity [ 42 , 46 ]. HTLV-1 infection induces IFI16 expression, and IFI16 interacts with the reverse transcription intermediate (RTI) ssDNA90 [ 47 ]. Of note, IFI16 enhances HTLV-1-induced innate immune responses through increased production of IFN-β, TNF-α, CCL5, and CXCL10 and promoting phosphorylation of IRF3 and p65 in a STING-dependent manner [ 47 ].…”

Section: Immune Sensors Of Htlv-1mentioning

confidence: 99%

“…HTLV-1 infection induces IFI16 expression, and IFI16 interacts with the reverse transcription intermediate (RTI) ssDNA90 [ 47 ]. Of note, IFI16 enhances HTLV-1-induced innate immune responses through increased production of IFN-β, TNF-α, CCL5, and CXCL10 and promoting phosphorylation of IRF3 and p65 in a STING-dependent manner [ 47 ]. IFI16 also limits HTLV-1 replication through inhibition of HTLV-1 protein expression [ 47 ].…”

Section: Immune Sensors Of 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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IFI16 regulates HTLV‐1 replication through promoting HTLV‐1 RTI‐induced innate immune responses

Cited by 11 publications

References 34 publications

Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

PCBP1 interacts with the HTLV-1 Tax oncoprotein to potentiate NF-κB activation

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

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