scholarly journals Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells

2020 ◽  
Vol 8 (11) ◽  
pp. 1790
Author(s):  
Anni Honkimaa ◽  
Bryn Kimura ◽  
Amir-Babak Sioofy-Khojine ◽  
Jake Lin ◽  
Jutta Laiho ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Persistent Infection ◽  
Prototype Strain ◽  
Structural Proteins ◽  
Capsid Region ◽  
Reading Frame ◽  
Pancreatic Cells ◽  
C Terminus ◽  
Generation Sequencing

Coxsackie B (CVB) viruses have been associated with type 1 diabetes. We have recently observed that CVB1 was linked to the initiation of the autoimmune process leading to type 1 diabetes in Finnish children. Viral persistency in the pancreas is currently considered as one possible mechanism. In the current study persistent infection was established in pancreatic ductal and beta cell lines (PANC-1 and 1.1B4) using four different CVB1 strains, including the prototype strain and three clinical isolates. We sequenced 5′ untranslated region (UTR) and regions coding for structural and non-structural proteins and the second single open reading frame (ORF) protein of all persisting CVB1 strains using next generation sequencing to identify mutations that are common for all of these strains. One mutation, K257R in VP1, was found from all persisting CVB1 strains. The mutations were mainly accumulated in viral structural proteins, especially at BC, DE, EF loops and C-terminus of viral capsid protein 1 (VP1), the puff region of VP2, the knob region of VP3 and infection-enhancing epitope of VP4. This showed that the capsid region of the viruses sustains various changes during persistency some of which could be hallmark(s) of persistency.

scholarly journals Next-Generation Sequencing Reveals ThatHLA-DRB3,-DRB4, and-DRB5May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes

Diabetes ◽  
2016 ◽  
Vol 65 (3) ◽  
pp. 710-718 ◽  
Author(s):  
Lue Ping Zhao ◽  
Shehab Alshiekh ◽  
Michael Zhao ◽  
Annelie Carlsson ◽  
Helena Elding Larsson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Next Generation Sequencing ◽  
Islet Autoantibodies ◽  
Next Generation ◽  
Childhood Type 1 Diabetes ◽  
Childhood Type ◽  
Generation Sequencing

scholarly journals Restoration of the Unfolded Protein Response in Pancreatic   Cells Protects Mice Against Type 1 Diabetes

2013 ◽  
Vol 5 (211) ◽  
pp. 211ra156-211ra156 ◽  
Author(s):  
F. Engin ◽  
A. Yermalovich ◽  
T. Nguyen ◽  
S. Hummasti ◽  
W. Fu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
Pancreatic Cells ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Quantitative Determination of Apoptosis of Pancreatic  -Cells in a Murine Model of Type 1 Diabetes Mellitus

2012 ◽  
Vol 53 (10) ◽  
pp. 1585-1591 ◽  
Author(s):  
A. Watanabe ◽  
K.-i. Nishijima ◽  
S. Zhao ◽  
Y. Zhao ◽  
Y. Tanaka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Quantitative Determination ◽  
Type 1 Diabetes Mellitus ◽  
Murine Model ◽  
Pancreatic Cells

scholarly journals C-terminal modification of the insulin B:11–23 peptide creates superagonists in mouse and human type 1 diabetes

2017 ◽  
Vol 115 (1) ◽  
pp. 162-167 ◽  
Author(s):  
Yang Wang ◽  
Tomasz Sosinowski ◽  
Andrey Novikov ◽  
Frances Crawford ◽  
David B. Neau ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell Activation ◽  
Posttranslational Modifications ◽  
Cell Activation ◽  
Nod Mice ◽  
Side Chain ◽  
C Terminus

A polymorphism at β57 in some major histocompatibility complex class II (MHCII) alleles of rodents and humans is associated with a high risk for developing type 1 diabetes (T1D). However, a highly diabetogenic insulin B chain epitope within the B:9–23 peptide is presented poorly by these alleles to a variety of mouse and human CD4 T cells isolated from either nonobese diabetic (NOD) mice or humans with T1D. We have shown for both species that mutations at the C-terminal end of this epitope dramatically improve presentation to these T cells. Here we present the crystal structures of these mutated peptides bound to mouse IAg7 and human HLA-DQ8 that show how the mutations function to improve T-cell activation. In both peptide binding grooves, the mutation of B:22R to E in the peptide changes a highly unfavorable side chain for the p9 pocket to an optimal one that is dependent on the β57 polymorphism, accounting for why these peptides bind much better to these MHCIIs. Furthermore, a second mutation of the adjacent B:21 (E to G) removes a side chain from the surface of the complex that is highly unfavorable for a subset of NOD mouse CD4 cells, thereby greatly enhancing their response to the complex. These results point out the similarities between the mouse and human responses to this B chain epitope in T1D and suggest there may be common posttranslational modifications at the C terminus of the peptide in vivo to create the pathogenic epitopes in both species.

scholarly journals BACH2, a Candidate Risk Gene for Type 1 Diabetes, Regulates Apoptosis in Pancreatic  -Cells via JNK1 Modulation and Crosstalk With the Candidate Gene PTPN2

Diabetes ◽  
2014 ◽  
Vol 63 (7) ◽  
pp. 2516-2527 ◽  
Author(s):  
L. Marroqui ◽  
I. Santin ◽  
R. S. Dos Santos ◽  
L. Marselli ◽  
P. Marchetti ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Candidate Gene ◽  
Risk Gene ◽  
Pancreatic Cells

scholarly journals Isolation and Abiotic Stress Resistance Analyses of a Catalase Gene fromIpomoea batatas(L.) Lam

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Bin Yong ◽  
Xiaoyan Wang ◽  
Pan Xu ◽  
Haiyan Zheng ◽  
Xueting Fei ◽  
...  
Keyword(s):  
Sweet Potato ◽  
Stress Responses ◽  
Reading Frame ◽  
Calmodulin Binding ◽  
C Terminus ◽  
Young Leaves ◽  
Quantitative Analyses ◽  
Encoding Gene ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

As an indicator of the antioxidant capability of plants, catalase can detoxify reactive oxygen species (ROS) generated by environmental stresses. Sweet potato is one of the top six most important crops in the world. However, its catalases remain largely unknown. In this study, a catalase encoding gene,IbCAT2(accession number: KY615708), was identified and cloned from sweet potato cv. Xushu 18. It contained a 1479 nucleotides’ open reading frame (ORF). S-R-L, Q-K-L, and a putative calmodulin binding domain were located at the C-terminus of IbCAT2, which suggests that IbCAT2 could be a peroxisomal catalase. Next-generation sequencing (NGS) based quantitative analyses showed thatIbCAT2was mainly expressed in young leaves and expanding tuberous roots under normal conditions. When exposed to 10% PEG6000 or 200 mmol/L NaCl solutions,IbCAT2was upregulated rapidly in the first 11 days and then downregulated, although different tissues showed different degree of change. Overexpression ofIbCAT2conferred salt and drought tolerance inEscherichia coliandSaccharomyces cerevisiae. The positive response ofIbCAT2to abiotic stresses suggested thatIbCAT2might play an important role in stress responses.

scholarly journals Extended nucleocapsid protein is cleaved from the Gag–Pol precursor of human immunodeficiency virus type 1

2001 ◽  
Vol 82 (3) ◽  
pp. 581-590 ◽  
Author(s):  
Nissim Chen ◽  
Abraham Morag ◽  
Nava Almog ◽  
Immanuel Blumenzweig ◽  
Orna Dreazin ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cleavage Site ◽  
Amino Acid Residues ◽  
Site Mutation ◽  
Reading Frame ◽  
C Terminus ◽  
Immunodeficiency Virus

Human immunodeficiency virus type 1 Gag and Gag–Pol precursors are translated from an mRNA which is indistinguishable from the full-length genomic RNA. The ratio of Gag to Gag–Pol polyproteins is approximately 20:1 and is controlled by a frameshift of the reading frame, which takes place downstream of the p7 nucleocapsid (NC) in the N terminus of the p1 peptide. The viral precursors Gag and Gag–Pol are cleaved by the virus-encoded protease (PR) into the structural proteins, and into p6Pol, PR, reverse transcriptase and integrase. Due to the frameshift event, the cleavage site at the C terminus of NC coded in the Gag frame (ERQAN-FLGKI) changes either to ERQANFLRED or ERQANFFRED. The results presented in this report demonstrate that the NC released from the Gag–Pol precursor is 8 amino acid residues longer than the NC cleaved from the Gag polyprotein. Our results also show that truncated Gag–Pol precursors bearing cleavage site mutation at the NC/p6Pol, and/or p6Pol/PR junctions, undergo autoprocessing in bacterial and eukaryotic cells, indicating that PR is active when part of the precursor.

scholarly journals Growth of Rotaviruses in Primary Pancreatic Cells

2002 ◽  
Vol 76 (18) ◽  
pp. 9537-9544 ◽  
Author(s):  
Barbara S. Coulson ◽  
Paul D. Witterick ◽  
Yan Tan ◽  
Marilyn J. Hewish ◽  
Joanne N. Mountford ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Mice ◽  
Children At Risk ◽  
Macaque Monkeys ◽  
Rotavirus Infection ◽  
Nonobese Diabetic ◽  
Pancreatic Cells ◽  
Nonobese Diabetic Mice

ABSTRACT Rotavirus infection in children at risk of developing type 1 diabetes has been temporally associated with development of pancreatic islet autoantibodies. In this study, nonobese diabetic mice were shown to be susceptible to rhesus rotavirus infection and pancreatic islets from nonobese diabetic mice, nonobese diabetes-resistant mice, fetal pigs, and macaque monkeys supported various degrees of rotavirus growth. Human rotaviruses replicated in monkey islets only. This islet susceptibility shows that rotavirus infection of the pancreas in vivo might be possible.

scholarly journals Next-generation sequencing for viruses in children with rapid-onset type 1 diabetes

Diabetologia ◽  
2013 ◽  
Vol 56 (8) ◽  
pp. 1705-1711 ◽  
Author(s):  
H.-S. Lee ◽  
◽  
T. Briese ◽  
C. Winkler ◽  
M. Rewers ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Next Generation Sequencing ◽  
Rapid Onset ◽  
Next Generation ◽  
Onset Type ◽  
Generation Sequencing
Sign in / Sign up

Export Citation Format

Share Document