eEF-2K Deficiency Boosts the Virus-Specific Effector CD8<sup>+</sup> T Cell Responses During Viral Infection

In this study, we revealed a critical role of eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, in regulating T cells during vaccinia virus (VACV) infection. We found that eEF-2K-deficient (eEF-2K⁻/⁻) mice exhibited a significantly higher proportion of VACV-s...

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Main Authors: Liqing Wang, Benny Shone Song, Rayansh Poojary, Xiaofang Xiong, Xingcong Ren, Jin-Ming Yang, Jianxun Song
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/1/26
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author Liqing Wang
Benny Shone Song
Rayansh Poojary
Xiaofang Xiong
Xingcong Ren
Jin-Ming Yang
Jianxun Song
author_facet Liqing Wang
Benny Shone Song
Rayansh Poojary
Xiaofang Xiong
Xingcong Ren
Jin-Ming Yang
Jianxun Song
author_sort Liqing Wang
collection DOAJ
description In this study, we revealed a critical role of eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, in regulating T cells during vaccinia virus (VACV) infection. We found that eEF-2K-deficient (eEF-2K⁻/⁻) mice exhibited a significantly higher proportion of VACV-specific effector CD8<sup>+</sup> T cells without compromising the development of VACV-specific memory CD8<sup>+</sup> T cells. RNA sequencing demonstrated that eEF-2K⁻/⁻ VACV-specific effector CD8<sup>+</sup> T cells had enhanced functionality, which improves their capacity to combat viral infection during the effector phase. Moreover, we identified tumor necrosis factor receptor-associated factor 3 (TRAF3) as a critical mediator of the stronger antiviral response observed in eEF-2K⁻/⁻ effector CD8<sup>+</sup> T cells. These findings suggest that targeting eEF-2K may provide a novel strategy to augmenting effector CD8<sup>+</sup> T cell responses against viral infections.
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spelling doaj-art-4806b76ea3a04db5972cd4896997de2e2025-01-24T13:52:18ZengMDPI AGViruses1999-49152024-12-011712610.3390/v17010026eEF-2K Deficiency Boosts the Virus-Specific Effector CD8<sup>+</sup> T Cell Responses During Viral InfectionLiqing Wang0Benny Shone Song1Rayansh Poojary2Xiaofang Xiong3Xingcong Ren4Jin-Ming Yang5Jianxun Song6Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USADepartment of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USAIn this study, we revealed a critical role of eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, in regulating T cells during vaccinia virus (VACV) infection. We found that eEF-2K-deficient (eEF-2K⁻/⁻) mice exhibited a significantly higher proportion of VACV-specific effector CD8<sup>+</sup> T cells without compromising the development of VACV-specific memory CD8<sup>+</sup> T cells. RNA sequencing demonstrated that eEF-2K⁻/⁻ VACV-specific effector CD8<sup>+</sup> T cells had enhanced functionality, which improves their capacity to combat viral infection during the effector phase. Moreover, we identified tumor necrosis factor receptor-associated factor 3 (TRAF3) as a critical mediator of the stronger antiviral response observed in eEF-2K⁻/⁻ effector CD8<sup>+</sup> T cells. These findings suggest that targeting eEF-2K may provide a novel strategy to augmenting effector CD8<sup>+</sup> T cell responses against viral infections.https://www.mdpi.com/1999-4915/17/1/26eEF-2Keffector CD8<sup>+</sup> T cellsvaccinia virus (VACV)T cell immunityTRAF3viral infection
spellingShingle Liqing Wang
Benny Shone Song
Rayansh Poojary
Xiaofang Xiong
Xingcong Ren
Jin-Ming Yang
Jianxun Song
eEF-2K Deficiency Boosts the Virus-Specific Effector CD8<sup>+</sup> T Cell Responses During Viral Infection
Viruses
eEF-2K
effector CD8<sup>+</sup> T cells
vaccinia virus (VACV)
T cell immunity
TRAF3
viral infection
title eEF-2K Deficiency Boosts the Virus-Specific Effector CD8<sup>+</sup> T Cell Responses During Viral Infection
title_full eEF-2K Deficiency Boosts the Virus-Specific Effector CD8<sup>+</sup> T Cell Responses During Viral Infection
title_fullStr eEF-2K Deficiency Boosts the Virus-Specific Effector CD8<sup>+</sup> T Cell Responses During Viral Infection
title_full_unstemmed eEF-2K Deficiency Boosts the Virus-Specific Effector CD8<sup>+</sup> T Cell Responses During Viral Infection
title_short eEF-2K Deficiency Boosts the Virus-Specific Effector CD8<sup>+</sup> T Cell Responses During Viral Infection
title_sort eef 2k deficiency boosts the virus specific effector cd8 sup sup t cell responses during viral infection
topic eEF-2K
effector CD8<sup>+</sup> T cells
vaccinia virus (VACV)
T cell immunity
TRAF3
viral infection
url https://www.mdpi.com/1999-4915/17/1/26
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