T Cell Epitopes in Coxsackievirus B4 Structural Proteins Concentrate in Regions Conserved between Enteroviruses

Marttila, Jane; Hyöty, Heikki; Vilja, Pekka; Härkönen, Taina; Alho, Annu; Roivainen, Merja; Hyypiä, Timo; Ilonen, Jorma

doi:10.1006/viro.2001.1259

Cited by 22 publications

(17 citation statements)

References 18 publications

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“…The present results relate to our previous results with synthetic peptides where fewer T-cell epitopes were identified in VP1 than in other capsid proteins (Marttila et al, 2002). Many factors including similarities between viral proteins, HLA restrictions of the dominant peptides and protein expression levels within cell during infections can contribute to the correlations or lack of them.…”

Section: Discussionsupporting

confidence: 86%

“…In the case of CV-B4, epitopes in the structural and 2C proteins have previously been mapped using CD4 + T-cell lines (Marttila et al, 2001(Marttila et al, , 2002, whilst the HLA class I-restricted CD8 + epitopes have been mapped in the 3C and 3D proteins of CV-B3 (Weinzierl et al, 2008). The latter study identified four CD8…”

Section: Discussionmentioning

confidence: 99%

“…Isolated cells were incubated with CV-B4 virus (strain JVB) antigen lysate (10 mg ml 21 ) in RPMI 1640 supplemented with 10 % human serum, 10 mg gentamicin sulphate ml 21 , 10 mM HEPES buffer and 3 % glutamine (10 ml ml 21 ). Preparation of the lysate antigen has been described previously (Marttila et al, 2002). The lysate virus was inactivated by incubation at 56 uC for 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…However, T-cell epitopes in the structural viral proteins (VPs) of CV-B4 have also been described. Conserved VP4 and VP2 proteins induce more responsiveness than the highly variable VP1, which is the most heterologous viral protein and is currently used for the typing of enteroviruses (Marttila et al, 2002;Oberste et al, 2003). Specific epitopes recognized by CD4 + T-cells have recently been identified in the 3D [viral RNA-dependent RNA polymerase (RdRp)] protein of human enterovirus 71 (Dang et al, 2014), whilst a previous study on coxsackievirus…”

Section: Introductionmentioning

confidence: 99%

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Elicitation of T-cell responses by structural and non-structural proteins of coxsackievirus B4

Bengs

Marttila

Susi

et al. 2015

Journal of General Virology

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Coxsackievirus B4 (CV-B4) belongs to the genus Enterovirus within the family Picornaviridae. To investigate target proteins recognized by T-cells in human enterovirus B infections, virus-encoded structural [VP0 (VP4 and VP2), VP1, VP3] and non-structural (2A, 2B, 2C, 3C and 3D) proteins were expressed and purified in Escherichia coli. Peripheral blood of 19 healthy adult donors was used to create enterovirus-specific T-cell lines by repeated stimulation with CV-B4 cell lysate antigen. T-cell lines responded in individual patterns, and responses to all purified proteins were observed. The most often recognized enteroviral protein was VP0, which is the fusion between the most conserved structural proteins, VP4 and VP2. T-cell responses to VP0 were detected in 15 of the 19 (79 %) donor lines. Non-structural 2C protein was recognized in 11 of the 19 (58 %) lines, and 11 of the 19 (58 %) lines also had a response to 3D protein. Furthermore, responses to other non-structural proteins (2A, 2B and 3C) were also detected. T-cell responses did not correlate clearly to the individual HLA-DR-DQ phenotype or the history of past coxsackie B virus infections of the donors.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Elicitation of T-cell responses by structural and non-structural proteins of coxsackievirus B4

Bengs

Marttila

Susi

et al. 2015

Journal of General Virology

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“…This phenomenon could be explained by immunological cross-protection induced by CVB3 and CVB6 against the diabetogenic effect of CVB1. Such cross-protection, most likely due to cell-mediated immunity, has been reported in other virus diseases, such as among different rotavirus, papillomavirus, and poliovirus types (33)(34)(35)(36)(37). Crossprotection is also supported by the increased CVB1-related risk in children who were infected by CVB1 but none of the protective serotypes.…”

Section: Discussionmentioning

confidence: 64%

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

Laitinen¹,

Honkanen

Pakkanen³

et al. 2014

Diabetes

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221

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The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes that could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study. The study participants comprised 183 case children testing persistently positive for at least two diabetes-predictive autoantibodies and 366 autoantibody-negative matched control children. Coxsackievirus B1 was associated with an increased risk of β-cell autoimmunity. This risk was strongest when infection occurred a few months before autoantibodies appeared and was attenuated by the presence of maternal antibodies against the virus. Two other coxsackieviruses, B3 and B6, were associated with a reduced risk, with an interaction pattern, suggesting immunological cross-protection against coxsackievirus B1. These results support previous observations suggesting that the group B coxsackieviruses are associated with the risk of type 1 diabetes. The clustering of the risk and protective viruses to this narrow phylogenetic lineage supports the biological plausibility of this phenomenon.

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Enteroviruses and type 1 diabetes

Varela-Calviño¹,

Peakman²

2003

Diabetes Metabolism Res

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The development of type 1 diabetes mellitus (T1DM) has been linked to exposure to environmental triggers, with Enteroviruses (EV) historically considered the prime suspects. Early serological studies suggested a link between EV infections and the development of T1DM and, though controversial, have been bolstered by more recent studies using more sensitive techniques such as direct detection of the EV genome by RT-PCR in peripheral blood. In this review, we consider the weight of evidence that EV can be considered a candidate trigger of T1DM, using three major criteria: (1) is EV infection associated with clinical T1DM, (2) can EV trigger the development of autoimmunity and (3) what would explain the putative association?

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T Cell Epitopes in Coxsackievirus B4 Structural Proteins Concentrate in Regions Conserved between Enteroviruses

Cited by 22 publications

References 18 publications

Elicitation of T-cell responses by structural and non-structural proteins of coxsackievirus B4

Elicitation of T-cell responses by structural and non-structural proteins of coxsackievirus B4

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

Enteroviruses and type 1 diabetes

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