HTLV-1's Foxy Strategy for Survival and Transmission

Higuchi, Yusuke; Yasunaga, Jun-ichirou; Matsuoka, Masao

doi:10.3389/fviro.2021.792659

Cited by 6 publications

(4 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, increasing Nrp1 expression might represent a second mechanism by which HBZ enhances TGF-β signaling. This signaling pathway is implicated in establishing the regulatory T-cell-like phenotype documented for most HTLV-1 infected cells [ 84 ]. It would be interesting to investigate this, and other potential effects of Nrp-1 related to HTLV-1 infection and pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Neuropilin-1 Inhibits HTLV-1 Infection

et al. 2023

View full text Add to dashboard Cite

Infection with human T-cell leukemia virus type 1 (HTLV-1) can produce a spectrum of pathological effects ranging from inflammatory disorders to leukemia. In vivo, HTLV-1 predominantly infects CD4+ T-cells. Infectious spread within this population involves the transfer of HTLV-1 virus particles from infected cells to target cells only upon cell-to-cell contact. The viral protein, HBZ, was found to enhance HTLV-1 infection through transcriptional activation of ICAM1 and MYOF, two genes that facilitate viral infection. In this study, we found that HBZ upregulates the transcription of COL4A1, GEM, and NRP1. COL4A1 and GEM are genes involved in viral infection, while NRP1, which encodes neuropilin 1 (Nrp1), serves as an HTLV-1 receptor on target cells but has no reported function on HTLV-1-infected cells. With a focus on Nrp1, cumulative results from chromatin immunoprecipitation assays and analyses of HBZ mutants support a model in which HBZ upregulates NRP1 transcription by augmenting recruitment of Jun proteins to an enhancer downstream of the gene. Results from in vitro infection assays demonstrate that Nrp1 expressed on HTLV-1-infected cells inhibits viral infection. Nrp1 was found to be incorporated into HTLV-1 virions, and deletion of its ectodomain removed the inhibitory effect. These results suggest that inhibition of HTLV-1 infection by Nrp1 is caused by the ectodomain of Nrp1 extended from virus particles, which may inhibit the binding of virus particles to target cells. While HBZ has been found to enhance HTLV-1 infection using cell-based models, there may be certain circumstances in which activation of Nrp1 expression negatively impacts viral infection, which is discussed.

show abstract

Section: Discussionmentioning

confidence: 99%

Upregulation of Neuropilin-1 Inhibits HTLV-1 Infection

et al. 2023

View full text Add to dashboard Cite

show abstract

“…However, because Tax exhibits strong immunogenicity, infected T cells expressing Tax are actively eliminated by Tax-specific CTLs [22,23]. At the onset of ATL, approximately 50% of cases do not show Tax expression due to methylation or the deletion of the 5 LTR region; thus, the selective proliferation of clones that are not attacked by CTLs is likely to be promoted [24]. In addition, recent studies have revealed that sense-side transcription leading to Tax expression occurs in transient bursts, even in the absence of genomic deletions or epigenetic changes in the provirus [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Understanding the Immunopathology of HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: A Comprehensive Review

Nakahata,

Enriquez-Vera,

Jahan

et al. 2023

Biomolecules

View full text Add to dashboard Cite

Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL). HTLV-1 carriers have a lifelong asymptomatic balance between infected cells and host antiviral immunity; however, 5–10% of carriers lose this balance and develop ATL. Coinfection with Strongyloides promotes ATL development, suggesting that the immunological status of infected individuals is a determinant of HTLV-1 pathogenicity. As CD4+ T cells play a central role in host immunity, the deregulation of their function and differentiation via HTLV-1 promotes the immune evasion of infected T cells. During ATL development, the accumulation of genetic and epigenetic alterations in key host immunity-related genes further disturbs the immunological balance. Various approaches are available for treating these abnormalities; however, hematopoietic stem cell transplantation is currently the only treatment with the potential to cure ATL. The patient’s immune state may contribute to the treatment outcome. Additionally, the activity of the anti-CC chemokine receptor 4 antibody, mogamulizumab, depends on immune function, including antibody-dependent cytotoxicity. In this comprehensive review, we summarize the immunopathogenesis of HTLV-1 infection in ATL and discuss the clinical findings that should be considered when developing treatment strategies for ATL.

show abstract

“…In addition, HTLV-1 is involved in the development of a variety of autoimmune diseases and several other inflammatory diseases, such as bronchiectasis, arthritis, infective dermatitis, myopathies, and multiple different uveitides ( 6 , 7 ). HTLV-1 is transmitted in various routes such as blood transfusion, intravenous injection, sexual contact, vertical transmission from mother to baby, breastfeeding, and organ transplant ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

Investigating the effect of MAP2K1 gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL)

Hosseini

Foroushani

Marjani

et al. 2023

IJM

View full text Add to dashboard Cite

Background and Objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals. Materials and Methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software. Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database. Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.

show abstract

HTLV-1's Foxy Strategy for Survival and Transmission

Cited by 6 publications

References 63 publications

Upregulation of Neuropilin-1 Inhibits HTLV-1 Infection

Upregulation of Neuropilin-1 Inhibits HTLV-1 Infection

Understanding the Immunopathology of HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: A Comprehensive Review

Investigating the effect of MAP2K1 gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL)

Contact Info

Product

Resources

About