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

2020 ◽  
Vol 8 (9) ◽  
pp. 1382
Author(s):  
William Klitz ◽  
Bo Niklasson
Keyword(s):  
Islets Of Langerhans ◽  
First Generation ◽  
Antiviral Treatment ◽  
Recent Onset ◽  
Bank Voles ◽  
Antiviral Compounds ◽  
Ljungan Virus ◽  
In The Wild ◽  
Treatment Of Diabetes ◽  
Single Disease Entity

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.

Genome characterisation of two Ljungan virus isolates from wild bank voles ( Myodes glareolus ) in Sweden

2015 ◽  
Vol 36 ◽  
pp. 156-164 ◽  
Author(s):  
Kieran C. Pounder ◽  
Phillip C. Watts ◽  
Bo Niklasson ◽  
Eva R.K. Kallio ◽  
Denise A. Marston ◽  
...  
Keyword(s):  
Myodes Glareolus ◽  
Bank Voles ◽  
Ljungan Virus ◽  
Virus Isolates

scholarly journals Patterns of ectoparasite infection in wild-caught and laboratory-bred cichlid fish, and their hybrids, implicate extrinsic rather than intrinsic causes of species differences in infection

Hydrobiologia ◽  
2020 ◽  
Author(s):  
Tiziana P. Gobbin ◽  
Ron Tiemersma ◽  
Giulia Leone ◽  
Ole Seehausen ◽  
Martine E. Maan
Keyword(s):  
Host Species ◽  
First Generation ◽  
Species Differences ◽  
Lake Victoria ◽  
Cichlid Fish ◽  
Laboratory Populations ◽  
Parasite Infections ◽  
In The Wild ◽  
Host Ecology ◽  
Differential Exposure

Abstract Parasite-mediated selection may initiate or enhance differentiation between host populations that are exposed to different parasite infections. Variation in infection among populations may result from differences in host ecology (thereby exposure to certain parasites) and/or intrinsic immunological traits. Species of cichlid fish, even when recently diverged, often differ in parasite infection, but the contributions of intrinsic and extrinsic causes are unknown. Here, we compare infection patterns between two closely related host species from Lake Victoria (genus Pundamilia), using wild-caught and first-generation laboratory-reared fish, as well as laboratory-reared hybrids. Three of the commonest ectoparasite species observed in the wild were also present in the laboratory populations. However, the infection differences between the host species as observed in the wild were not maintained in laboratory conditions. In addition, hybrids did not differ in infection from either parental species. These findings suggest that the observed species differences in infection in the wild might be mainly driven by ecology-related effects (i.e. differential exposure), rather than by intrinsic species differences in immunological traits. Thus, while there is scope for parasite-mediated selection in Pundamilia in the wild, it has apparently not yet generated divergent evolutionary responses and may not enhance assortative mating among closely related species.

scholarly journals Development of Type 1 Diabetes in Wild Bank Voles Associated With Islet Autoantibodies and the Novel Ljungan Virus

2003 ◽  
Vol 4 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Bo Niklasson ◽  
Knud E. Heller ◽  
Bryan Schønecker ◽  
Mogens Bildsøe ◽  
Terri Daniels ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Age At Onset ◽  
Clethrionomys Glareolus ◽  
Acid Decarboxylase ◽  
Specific Lysis ◽  
Bank Voles ◽  
Ljungan Virus ◽  
Group A ◽  
Group B

Wild bank voles (Clethrionomys glareolus) may develop diabetes in laboratory captivity. The aim of this study was to test whether bank voles develop type 1 diabetes in association with Ljungan virus. Two groups of bank voles were analyzed for diabetes, pancreas histology, autoantibodies to glutamic acid decarboxylase (GAD65), IA-2, and insulin by standardized radioligand-binding assays as well as antibodies to in vitro transcribed and translated Ljungan virus antigens. Group A represented 101 trapped bank voles, which were screened for diabetes when euthanized within 24 hours of capture. Group B represented 67 bank voles, which were trapped and kept in the laboratory for 1 month before being euthanized. Group A bank voles did not have diabetes. Bank voles in group B (22/67; 33%) developed diabetes due to specific lysis of pancreatic islet beta cells. Compared to nondiabetic group B bank voles, diabetic animals had increased levels of GAD65 (P< .0001), IA-2 (P< .0001), and insulin (P= .03) autoantibodies. Affected islets stained positive for Ljungan virus, a novel picorna virus isolated from bank voles. Ljungan virus inoculation of nondiabetic wild bank voles induced beta-cell lysis. Compared to group A bank voles, Ljungan virus antibodies were increased in both nondiabetic (P< .0001) and diabetic (P= .0015) group B bank voles. Levels of Ljungan virus antibodies were also increased in young age at onset of newly diagnosed type 1 diabetes in children (P< .01). These findings support the hypothesis that the development of type 1 diabetes in captured wild bank voles is associated with Ljungan virus. It is speculated that bank voles may have a possible zoonotic role as a reservoir and vector for virus that may contribute to the incidence of type 1 diabetes in humans.

Islet autoantibodies present in association with Ljungan virus infection in bank voles (Myodes glareolus) in northern Sweden

2016 ◽  
Vol 89 (1) ◽  
pp. 24-31 ◽  
Author(s):  
Anna Warvsten ◽  
Martin Björnfors ◽  
Michael Arvidsson ◽  
Fariba Vaziri-Sani ◽  
Ida Jönsson ◽  
...  
Keyword(s):  
Virus Infection ◽  
Islet Autoantibodies ◽  
Myodes Glareolus ◽  
Northern Sweden ◽  
Bank Voles ◽  
Ljungan Virus

scholarly journals Evolutionary Relationships of Ljungan Virus Variants Circulating in Multi-Host Systems across Europe

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1317
Author(s):  
Chiara Rossi ◽  
Nicola Zadra ◽  
Cristina Fevola ◽  
Frauke Ecke ◽  
Birger Hörnfeldt ◽  
...  
Keyword(s):  
Small Mammals ◽  
Rna Virus ◽  
Natural Populations ◽  
Purifying Selection ◽  
Myodes Glareolus ◽  
Evolutionary Relationships ◽  
Mammal Species ◽  
Bank Voles ◽  
Ljungan Virus ◽  
Small Mammal Species

The picornavirus named ‘Ljungan virus’ (LV, species Parechovirus B) has been detected in a dozen small mammal species from across Europe, but detailed information on its genetic diversity and host specificity is lacking. Here, we analyze the evolutionary relationships of LV variants circulating in free-living mammal populations by comparing the phylogenetics of the VP1 region (encoding the capsid protein and associated with LV serotype) and the 3Dpol region (encoding the RNA polymerase) from 24 LV RNA-positive animals and a fragment of the 5′ untranslated region (UTR) sequence (used for defining strains) in sympatric small mammals. We define three new VP1 genotypes: two in bank voles (Myodes glareolus) (genotype 8 from Finland, Sweden, France, and Italy, and genotype 9 from France and Italy) and one in field voles (Microtus arvalis) (genotype 7 from Finland). There are several other indications that LV variants are host-specific, at least in parts of their range. Our results suggest that LV evolution is rapid, ongoing and affected by genetic drift, purifying selection, spillover and host evolutionary history. Although recent studies suggest that LV does not have zoonotic potential, its widespread geographical and host distribution in natural populations of well-characterized small mammals could make it useful as a model for studying RNA virus evolution and transmission.

scholarly journals Molecular Analysis of Three Ljungan Virus Isolates Reveals a New, Close-to-Root Lineage of the Picornaviridae with a Cluster of Two Unrelated 2A Proteins

2002 ◽  
Vol 76 (17) ◽  
pp. 8920-8930 ◽  
Author(s):  
Susanne Johansson ◽  
Bo Niklasson ◽  
Jacob Maizel ◽  
Alexander E. Gorbalenya ◽  
A. Michael Lindberg
Keyword(s):  
Untranslated Region ◽  
Comparative Sequence Analysis ◽  
Clethrionomys Glareolus ◽  
Amino Acid Residues ◽  
Hydrophobic Residues ◽  
Conserved Sequence ◽  
Bank Voles ◽  
Ljungan Virus ◽  
Encephalomyelitis Virus ◽  
Virus Isolates

ABSTRACT Ljungan virus (LV) is a suspected human pathogen recently isolated from bank voles (Clethrionomys glareolus). In the present study, it is revealed through comparative sequence analysis that three newly determined Swedish LV genomes are closely related and possess a deviant picornavirus-like organization: 5′ untranslated region-VP0-VP3-VP1-2A1-2A2-2B-2C-3A-3B-3C-3D-3′ untranslated region. The LV genomes and the polyproteins encoded by them exhibit several exceptional features, such as the absence of a predicted maturation cleavage of VP0, a conserved sequence determinant in VP0 that is typically found in VP1 of other picornaviruses, and a cluster of two unrelated 2A proteins. The 2A1 protein is related to the 2A protein of cardio-, erbo-, tescho-, and aphthoviruses, and the 2A2 protein is related to the 2A protein of parechoviruses, kobuviruses, and avian encephalomyelitis virus. The unprecedented association of two structurally different 2A proteins is a feature never previously observed among picornaviruses and implies that their functions are not mutually exclusive. Secondary polyprotein processing of the LV polyprotein is mediated by proteinase 3C (3Cpro) possessing canonical affinity to Glu and Gln at the P1 position and small amino acid residues at the P1′ position. In addition, LV 3Cpro appears to have unique substrate specificity to Asn, Gln, and Asp and to bulky hydrophobic residues at the P2 and P4 positions, respectively. Phylogenetic analysis suggests that LVs form a separate division, which, together with the Parechovirus genus, has branched off the picornavirus tree most closely to its root. The presence of two 2A proteins indicates that some contemporary picornaviruses with a single 2A may have evolved from the ancestral multi-2A picornavirus.

scholarly journals Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp14/nsp10 Exoribonuclease

2021 ◽  
Author(s):  
Clovis Basier ◽  
Souradeep Basu ◽  
Rupert Beale ◽  
Agustina P Bertolin ◽  
Berta Canal ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Genome Replication ◽  
Economic Costs ◽  
Cell Culture Model ◽  
Antiviral Compounds ◽  
Biochemical Assays ◽  
Culture Model ◽  
Viral Genome Replication ◽  
Great Pressure

SARS-CoV-2 is a coronavirus that emerged in 2019 and rapidly spread across the world causing a deadly pandemic with tremendous social and economic costs. Healthcare systems worldwide are under great pressure, and there is urgent need for effective antiviral treatments. The only currently approved antiviral treatment for COVID-19 is remdesivir, an inhibitor of viral genome replication. SARS-CoV-2 proliferation relies on the enzymatic activities of the non-structural proteins (nsp), which makes them interesting targets for the development of new antiviral treatments. With the aim to identify novel SARS-CoV-2 antivirals, we have purified the exoribonuclease/methyltransferase (nsp14) and its cofactor (nsp10) and developed biochemical assays compatible with high-throughput approaches to screen for exoribonuclease inhibitors. We have screened a library of over 5000 commercial compounds and identified patulin and aurintricarboxylic acid (ATA) as inhibitors of nsp14 exoribonuclease in vitro. We found that patulin and ATA inhibit replication of SARS-CoV-2 in a VERO E6 cell-culture model. These two new antiviral compounds will be valuable tools for further coronavirus research as well as potentially contributing to new therapeutic opportunities for COVID-19.

scholarly journals Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp14/nsp10 exoribonuclease

2021 ◽  
Vol 478 (13) ◽  
pp. 2445-2464
Author(s):  
Berta Canal ◽  
Allison W. McClure ◽  
Joseph F. Curran ◽  
Mary Wu ◽  
Rachel Ulferts ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Genome Replication ◽  
Economic Costs ◽  
Cell Culture Model ◽  
Antiviral Compounds ◽  
Biochemical Assays ◽  
Culture Model ◽  
Viral Genome Replication ◽  
Great Pressure

SARS-CoV-2 is a coronavirus that emerged in 2019 and rapidly spread across the world causing a deadly pandemic with tremendous social and economic costs. Healthcare systems worldwide are under great pressure, and there is an urgent need for effective antiviral treatments. The only currently approved antiviral treatment for COVID-19 is remdesivir, an inhibitor of viral genome replication. SARS-CoV-2 proliferation relies on the enzymatic activities of the non-structural proteins (nsp), which makes them interesting targets for the development of new antiviral treatments. With the aim to identify novel SARS-CoV-2 antivirals, we have purified the exoribonuclease/methyltransferase (nsp14) and its cofactor (nsp10) and developed biochemical assays compatible with high-throughput approaches to screen for exoribonuclease inhibitors. We have screened a library of over 5000 commercial compounds and identified patulin and aurintricarboxylic acid (ATA) as inhibitors of nsp14 exoribonuclease in vitro. We found that patulin and ATA inhibit replication of SARS-CoV-2 in a VERO E6 cell-culture model. These two new antiviral compounds will be valuable tools for further coronavirus research as well as potentially contributing to new therapeutic opportunities for COVID-19.

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