Human neurotropic polyomavirus, JC virus, agnoprotein targets mitochondrion and modulates its functions

Saxena, Reshu; Saribas, Sami; Jadiya, Pooja; Tomar, Dhanendra; Kaminski, Rafal; Elrod, John W.; Safak, Mahmut

doi:10.1016/j.virol.2020.11.004

Cited by 8 publications

(7 citation statements)

References 109 publications

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“…Recently, the polyomavirus agnoprotein was shown to target mitochondria and modulate their functions. 31 The BK polyomavirus disrupts the mitochondrial network and membrane potential when expressing the 66aa-long agnoprotein in the late viral life cycle. This agnoprotein impairs nuclear interferon regulatory factor 3 (IRF3)-translocation, impairs interferon-beta expression, and promotes mitophagy, thereby allowing the polyomavirus to evade innate immune sensing.…”

Section: Discussionmentioning

confidence: 99%

Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology

Loon

Lamarthée

Loor

et al. 2022

Kidney International

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Section: Discussionmentioning

confidence: 99%

Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology

Loon

Lamarthée

Loor

et al. 2022

Kidney International

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“…The interaction dissociated FEZ1 from the microtubules and inhibited FEZ1-facilitated neurite outgrowth. Saxena et al (76) reported that the mitochondrial targeting sequence and dimerization domain of agnoprotein mediate mitochondrial localization, where agnoprotein decreased the respiration rate, mitochondrial membrane potential, and ATP production while increasing ROS production and Ca 2+ uptake.…”

Section: Agnoproteinmentioning

confidence: 99%

The oncogenic roles of JC polyomavirus in cancer

Zheng

Xue

Zhang³

2022

Front. Oncol.

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JC polyomavirus (JCPyV) belongs to the human polyomavirus family. Based on alternative splicing, the early region encodes the large and small T antigens, while the late region encodes the capsid structural proteins (VP1, VP2, and VP3) and the agnoprotein. The regulatory transcription factors for JCPyV include Sp1, TCF-4, DDX1, YB-1, LCP-1, Purα, GF-1, and NF-1. JCPyV enters tonsillar tissue through the intake of raw sewage, inhalation of air droplets, or parent-to-child transmission. It persists quiescently in lymphoid and renal tissues during latency. Both TGF-β1 and TNF-α stimulates JCPyV multiplication, while interferon-γ suppresses the process. The distinct distribution of caspid receptors (α-2, 6-linked sialic acid, non-sialylated glycosaminoglycans, and serotonin) determines the infection capabilities of JCPyV virions, and JCPyV entry is mediated by clathrin-mediated endocytosis. In permissive cells, JCPyV undergoes lytic proliferation and causes progressive multifocal leukoencephalopathy, while its DNA is inserted into genomic DNA and leads to carcinogenesis in non-permissive cells. T antigen targets p53, β-catenin, IRS, Rb, TGF-β1, PI3K/Akt and AMPK signal pathways in cancer cells. Intracranial injection of T antigen into animals results in neural tumors, and transgenic mice develop neural tumors, lens tumor, breast cancer, gastric, Vater’s, colorectal and pancreatic cancers, insulinoma, and hepatocellular carcinoma. Additionally, JCPyV DNA and its encoded products can be detected in the brain tissues of PML patients and brain, oral, esophageal, gastric, colorectal, breast, cervical, pancreatic, and hepatocellular cancer tissues. Therefore, JCPyV might represent an etiological risk factor for carcinogenesis and should be evaluated for early prevention, diagnosis, and treatment of cancers.

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“…The early region encodes T antigen ( Reiss and Khalili, 2003 ), a large phosphoprotein that binds to the viral replication region to promote double helix unwinding and recruitment of DNA synthesis proteins. The late region encodes the capsid structural proteins VP1, VP2 and, VP3 and agnoprotein ( Reiss and Khalili, 2003 ; Saxena et al, 2021 ). Serologically, there is asymptomatic JCV infection in 80–90% of the adult population ( Ahye et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…JCV enters the human body through both digestive and respiratory tracts and persists quiescent in the kidney and lymphoid tissues ( White and Khalili, 2005 ; Delbue et al, 2017 ; Dwyer et al, 2021 ). However, it may be activated under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy (PML) ( Reiss and Khalili, 2003 ; Delbue et al, 2017 ; Ahye et al, 2020 ; Dwyer et al, 2021 ; Saxena et al, 2021 ). During permissive infection, replication of viral DNA can cause lytic infection, but in non-permissive cells, either abortive infection or cell transformation is the outcome ( Delbue et al, 2017 ; Ahye et al, 2020 ; Saxena et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…However, it may be activated under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy (PML) ( Reiss and Khalili, 2003 ; Delbue et al, 2017 ; Ahye et al, 2020 ; Dwyer et al, 2021 ; Saxena et al, 2021 ). During permissive infection, replication of viral DNA can cause lytic infection, but in non-permissive cells, either abortive infection or cell transformation is the outcome ( Delbue et al, 2017 ; Ahye et al, 2020 ; Saxena et al, 2021 ). JCV can transform cells, which display rapid growth and division, prolongation of lifespan, anchorage-dependent growth, chromosomal instability, and dense foci formation in culture ( Eash et al, 2004 ; White and Khalili, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

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The Oncogenic Roles of JC Virus T Antigen in Breast Carcinogenesis

Zheng

Ying

Cui

et al. 2021

Front. Mol. Biosci.

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Purpose: JC virus (JCV) infects 80–90% of the population and results in progressive multifocal leukoencephalopathy upon immunodeficiency. The study aimed to pathologically clarify the oncogenic roles of T antigen in human breast cancers.Methods: Breast cancer, dysplasia, and normal tissues were examined for T antigen of JCV by nested and real-time PCR. The positive rate or copy number of T antigen was compared with clinicopathological parameters of breast cancer. JCV existence was morphologically detected by immunohistochemistry and in situ PCR. T antigen was examined by Western blot using frozen samples of breast cancer and paired normal tissues.Results: According to nested PCR, the positive rate of breast ductal or lobular carcinoma was lower than that of normal tissue (p < 0.05). T antigen existence was negatively correlated with E-cadherin expression and triple-negative breast cancer (p < 0.05), but positively correlated with lymph node metastasis and estrogen receptor and progestogen receptor expression (p < 0.05). Quantitative PCR showed that JCV copies were gradually decreased from normal, dysplasia to cancer tissues (p < 0.05). JCV T antigen copy number was lower in ductal adenocarcinoma than in normal tissue (p < 0.05), in line with in situ PCR and immunohistochemistry. JCV copies were negatively correlated with tumor size and E-cadherin expression (p < 0.05), but positively correlated with G grading of breast cancer (p < 0.05). Western blot also indicated weaker T antigen expression in breast cancer than normal tissues (p < 0.05).Conclusion: JCV T antigen might play an important role in breast carcinogenesis. It can be employed as a molecular marker for the differentiation and aggressive behaviors of breast cancer.

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Human neurotropic polyomavirus, JC virus, agnoprotein targets mitochondrion and modulates its functions

Cited by 8 publications

References 109 publications

Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology

Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology

The oncogenic roles of JC polyomavirus in cancer

The Oncogenic Roles of JC Virus T Antigen in Breast Carcinogenesis

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