The BioBreeding rat diabetes model is infected with Ljungan virus

Niklasson, Bo; Hultman, Thomas; Kallies, René; Niedrig, Matthias; Nilsson, Rikard; Berggren, PO; Juntti‐Berggren, Lisa; Efendić, Suad; Lernmark, Åke; Klitz, William

doi:10.1007/s00125-007-0659-3

Cited by 22 publications

(4 citation statements)

References 7 publications

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Section: Ljungan Virus Associated With Diabetes In Animalsmentioning

confidence: 63%

“…We observed the LV antigen in the islets of Langerhans in diabetic BB rats [35], thus suggesting LV infection intrinsic to the strain. This was followed by the finding that diabetes onset could be postponed using the antiviral compounds Pleconaril and Ribavirin [23,35]. We later extended our antiviral investigations using treatment with Pleconaril and an experimental antiviral kinase inhibitor APO-N039.…”

Section: Ljungan Virus Associated With Diabetes In Animalsmentioning

confidence: 63%

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Extending the Enterovirus Lead: Could a Related Picornavirus be Responsible for Diabetes in Humans?

Klitz

Niklasson

2020

Microorganisms

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We found an association between the abundance of rodents in the wild and onset of type 1 diabetes (T1D) in humans. A picornavirus named Ljungan virus (LV) was subsequently isolated from wild bank voles. Both picornavirus-like particles detected by electron microscopy and LV antigen visualized by immunohistochemistry was seen in islets of Langerhans in diabetic wild bank voles. LV antigen has also been found in islets of Langerhans in a patient with recent onset of T1D and in the commonly used Bio Breeding (BB) T1D rat model. We discuss the possibility of T1D and type 2 diabetes (T2D) as parts of a single disease entity. Antiviral compounds directed against picornavirus have been found to be an effective treatment of diabetes in BB rats. We propose using the same currently available antiviral compounds in clinical trials in humans. Antiviral treatment would have the potential to be both proof of concept for involvement of a picornavirus in diabetes pathogenesis and also present a first-generation therapy.

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Section: Ljungan Virus Associated With Diabetes In Animalsmentioning

confidence: 63%

Section: Ljungan Virus Associated With Diabetes In Animalsmentioning

confidence: 63%

Extending the Enterovirus Lead: Could a Related Picornavirus be Responsible for Diabetes in Humans?

Klitz

Niklasson

2020

Microorganisms

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“…Ljungan virus (LV), first isolated from a bank vole ( Myodes glareolus ) by the river Ljungan in Northern Sweden, was defined as a Parechovirus in the family Picornaviridae [1, 2]. The isolation of the 87–012 virus was followed by characterization of several different LV strains from humans, voles, other rodents, and birds [3–8]. However, it is unclear to what extent LV infection in humans causes symptoms characteristic of Parechovirus .…”

Section: Introductionmentioning

confidence: 99%

Neutralizing Ljungan virus antibodies in children with newly diagnosed type 1 diabetes

Lundstig

McDonald

Maziarz

et al. 2021

Journal of General Virology

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Ljungan virus (LV), a Parechovirus of the Picornavirus family, first isolated from a bank vole at the Ljungan river in Sweden, has been implicated in the risk for autoimmune type 1 diabetes. An assay for neutralizing Ljungan virus antibodies (NLVA) was developed using the original 87–012 LV isolate. The goal was to determine NLVA titres in incident 0–18 years old newly diagnosed type 1 diabetes patients (n=67) and school children controls (n=292) from Jämtland county in Sweden. NLVA were found in 41 of 67 (61 %) patients compared to 127 of 292 (44 %) controls (P=0.009). In the type 1 diabetes patients, NLVA titres were associated with autoantibodies to glutamic acid decarboxylase (GADA) (P=0.023), but not to autoantibodies against insulin (IAA) or islet antigen-2 (IA-2A). The NLVA assay should prove useful for further investigations to determine levels of LV antibodies in patients and future studies to determine a possible role of LV in autoimmune type 1 diabetes.

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“…The onset of symptomatic diabetes in BB rats has a predictable and narrow time frame, providing an excellent opportunity to study the impact of treatment before, during or after disease onset. We previously reported the observation that LV antigen is present in the islets of Langerhans in BB rats at the time of diabetes onset [ 72 ]. This observation was followed by experiments to see if diabetes onset could be postponed, stopped or reversed using antiviral compounds.…”

Section: Discussionmentioning

confidence: 99%

Picornavirus May Be Linked to Parkinson’s Disease through Viral Antigen in Dopamine-Containing Neurons of Substantia Nigra

et al. 2022

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Parkinson’s disease (PD) is a neurodegenerative disease linked with the loss of dopaminergic neurons in the brain region called substantia nigra and caused by unknown pathogenic mechanisms. Two currently recognized prominent features of PD are an inflammatory response manifested by glial reaction and T-cell infiltration, as well as the presence of various toxic mediators derived from activated glial cells. PD or parkinsonism has been described after infection with several different viruses and it has therefore been hypothesized that a viral infection might play a role in the pathogenesis of the disease. We investigated formalin-fixed post-mortem brain tissue from 9 patients with Parkinson’s disease and 11 controls for the presence of Ljungan virus (LV) antigen using a polyclonal antibody against the capsid protein of this recently identified picornavirus with neurotropic properties, suspected of being both a human and an animal pathogen. Evidence of viral antigen was found in 7 out of 9 Parkinson’s disease cases and in only 1 out of 11 controls (p = 0.005). The picornavirus antigen was present in dopamine-containing neurons of the substantia nigra. We propose that LV or an LV-related virus initiates the pathological process underlying sporadic PD. LV-related picornavirus antigen has also been reported in patients with Alzheimer’s disease. Potentially successful antiviral treatment in Alzheimer’s disease suggests a similar treatment for Parkinson's disease. Amantadine, originally developed as an antiviral drug against influenza infection, has also been used for symptomatic treatment of patients with PD for more than 50 years and is still commonly used by neurologists today. The fact that amantadine also has an antiviral effect on picornaviruses opens the question of this drug being re-evaluated as potential PD therapy in combination with other antiviral compounds directed against picornaviruses.

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The BioBreeding rat diabetes model is infected with Ljungan virus

Cited by 22 publications

References 7 publications

Extending the Enterovirus Lead: Could a Related Picornavirus be Responsible for Diabetes in Humans?

Extending the Enterovirus Lead: Could a Related Picornavirus be Responsible for Diabetes in Humans?

Neutralizing Ljungan virus antibodies in children with newly diagnosed type 1 diabetes

Picornavirus May Be Linked to Parkinson’s Disease through Viral Antigen in Dopamine-Containing Neurons of Substantia Nigra

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