Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab

Flores, José de Jesús Vargas; Anguiano, O.; Rivas‐Alonso, Verónica; González-Conchillos, H.; Pérez-Saldívar, Miriam; Sotelo, Julio; Magaña-Maldonado, Roxana; Quiñones, Silvia Muñoz; Corona, Teresa; Olivares, Heidi; Hernández-González, Olivia; Martı́nez-Palomo, Adolfo; Trevino, Ingrid; Ordóñez, Graciela

doi:10.1016/j.msard.2021.103266

Cited by 2 publications

(1 citation statement)

References 24 publications

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“…Point mutations in VP1 can influence virion binding to cellular glycan receptors and their recognition by polyomavirusspecific antibodies (81). Mutation 186G!C (Lys!Asp) in the VP1 gene could predispose MS patients undergoing treatment with natalizumab to PML (82). A deletion of the C-terminal 10 bp of VP1 is closely linked to lytic infection of granule cell neurons and atrophy in the cerebellum of an HIV/PML patient (83).…”

Section: Caspidsmentioning

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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Section: Caspidsmentioning

confidence: 99%

The oncogenic roles of JC polyomavirus in cancer

Zheng

Xue

Zhang³

2022

Front. Oncol.

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Analysis of potentially modifiable risk factors of multiple sclerosis

Lipska

2024

Aktualn Neurol

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Multiple sclerosis, also known as sclerosis multiplex, is a chronic autoimmune disease of the central nervous system that occurs in over 2.9 millions individuals worldwide, most commonly in young to middle-aged adults, with a greater prevalence in females than males and in higher latitudes. There are different types of multiple sclerosis, varying in the presence and frequency of relapses and remissions. Various risk factors for the disorder have been identified as well – both modifiable and unmodifiable. Although many remain elusive, there are multiple theories regarding them. The causes of multiple sclerosis are yet to be established but a family history of the disease may increase the risk, and also environmental factors are believed to play a role. This paper focuses on the potentially modifiable factors. The most common theory seems to postulate an association between the disorder and viral infections, especially in individuals with Epstein–Barr virus infection, but also human herpesvirus 6, varicella-zoster virus, cytomegalovirus, or John Cunningham virus. Other risk factors include vitamin D insufficiency, or even its low levels, as multiple sclerosis is more frequent in higher latitudes. Obesity, especially during childhood and adolescence, can also be a risk factor of so-called paediatric-onset multiple sclerosis. Obesity is also linked to a higher severity of multiple sclerosis in adults. Risk factors associated with a potentially lower risk, or even some positive effects, include alcohol and caffeine consumption, as well as smoking and oral tobacco use.

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Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab

Cited by 2 publications

References 24 publications

The oncogenic roles of JC polyomavirus in cancer

The oncogenic roles of JC polyomavirus in cancer

Analysis of potentially modifiable risk factors of multiple sclerosis

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