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Published on: July 15, 2019
Elicitation of T-cell responses by structural and non-structural proteins of coxsackievirus B4
Suvi Bengs1,2, Jane Marttila2, Petri Susi3,1
1Department of Virology, University of Turku, Turku, Finland.
Abstract:
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.
Insights
Researchers identified key Coxsackievirus B4 (CV-B4) proteins recognized by T-cells in human enterovirus infections. The structural VP0 protein was most frequently targeted, highlighting its importance in T-cell immune responses to enteroviruses.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Coxsackievirus B4 (CV-B4) is an enterovirus implicated in various human diseases.
- Understanding T-cell recognition of viral proteins is crucial for developing effective immune strategies against enterovirus infections.
Purpose of the Study:
- To identify specific CV-B4 viral proteins recognized by T-cells in healthy adults.
- To characterize T-cell responses to both structural and non-structural CV-B4 proteins.
Main Methods:
- Expression and purification of CV-B4 structural (VP0, VP1, VP3) and non-structural (2A, 2B, 2C, 3C, 3D) proteins using Escherichia coli.
- Generation of enterovirus-specific T-cell lines from peripheral blood of 19 healthy donors.
- Assessment of T-cell responses to purified viral proteins and CV-B4 cell lysate antigen.
Main Results:
- T-cell lines exhibited diverse individual response patterns to CV-B4 proteins.
- The structural VP0 protein (VP4 and VP2) was the most frequently recognized, with T-cell responses detected in 79% of donor lines.
- Non-structural proteins 2C and 3D were also significantly recognized (58% of lines each), along with other non-structural proteins (2A, 2B, 3C).
- T-cell responses did not correlate with HLA-DR-DQ phenotype or prior coxsackie B virus infection history.
Conclusions:
- CV-B4 infection elicits T-cell responses targeting multiple viral proteins, with VP0 being a major immunodominant antigen.
- Non-structural proteins like 2C and 3D also contribute to the T-cell mediated immune response.
- These findings provide insights into the T-cell epitope landscape of CV-B4, relevant for vaccine development and understanding viral pathogenesis.
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