The unique immune evasion mechanisms of the mpox virus and their implication for developing new vaccines and immunotherapies

Dong Fang; Yan Liu; Dou Dou; Bin Su

doi:10.1016/j.virs.2024.08.008

October 2024

. doi: 10.1016/j.virs.2024.08.008

Citation: Dong Fang, Yan Liu, Dou Dou, Bin Su. The unique immune evasion mechanisms of the mpox virus and their implication for developing new vaccines and immunotherapies .VIROLOGICA SINICA, 2024, 39(5) : 709-718. http://dx.doi.org/10.1016/j.virs.2024.08.008

猴痘病毒独特的免疫逃避机制及其对开发新型疫苗和免疫疗法的意义

方冬 ^a ,
刘炎 ^b ,
窦豆 ^a ,
粟斌 ^a,b,c,,

cstr: 32224.14.j.virs.2024.08.008

a. 国家自然科学基金委员会, 医学科学部, 北京 100085;
b. 首都医科大学附属北京佑安医院, 艾滋病研究北京市重点实验室, 北京 100069;
c. 首都医科大学附属北京佑安医院, 中心实验室, 北京 100069

通讯作者： 粟斌, binsu@ccmu.edu.cn
收稿日期： 2024-05-11
录用日期： 2024-08-20

摘要

猴痘是一种由正痘病毒属的猴痘病毒（mpox virus, MPXV）引起的人畜共患传染性疾病。自2022年以来，猴痘病毒对全球公共卫生构成了重大威胁，尤其是在西半球出现了数千例病例后，世界卫生组织宣布进入紧急状态。痘病毒与人类广泛的共同进化史，使这些病毒发展出了对抗人类免疫系统的复杂机制。特别是猴痘病毒，可通过独特的免疫逃逸策略对抗多种免疫因素，给治疗带来了相当大的挑战。这种情况在普通人群停止常规天花疫苗接种之后尤其突出。在本综述中，我们首先讨论了猴痘病毒的入侵和早期感染特征，接着介绍了猴痘病毒逃避固有免疫和适应性免疫反应的机制。研究发现，两个caspase-1抑制蛋白和一个PKR逃逸相关蛋白是调节MPXV感染期间免疫环境的重要枢纽。在适应性免疫方面，猴痘病毒表现出独特而强大的T细胞抑制能力，从而全面重塑宿主免疫环境。病毒包膜也对抗体和补体系统的中和作用带来了挑战。猴痘病毒独特的免疫逃逸机制使得基于多表位和核酸的新型疫苗成为极具前景的研究方向。最后，我们简要讨论了猴痘病毒感染对免疫抑制患者的影响以及目前的疫苗研发现状。本综述旨在为开发新的猴痘免疫疗法提供有价值的信息。
- 猴痘病毒
- , 免疫反应
- , 免疫逃逸
- , 免疫病理学
- , DNA感应

The unique immune evasion mechanisms of the mpox virus and their implication for developing new vaccines and immunotherapies

Dong Fang ^a ,
Yan Liu ^b ,
Dou Dou ^a ,
Bin Su ^a,b,c,,

a. Department of Health Sciences, National Natural Science Foundation of China, Beijing, 100085, China;
b. Beijing Key Laboratory for HIV/AIDS Research, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China;
c. Central Laboratory, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China

Corresponding author: Bin Su, binsu@ccmu.edu.cn
Received Date: 11 May 2024
Accepted Date: 20 August 2024

Abstract

Mpox is an infectious and contagious zoonotic disease caused by the mpox virus (MPXV), which belongs to the genus Orthopoxvirus. Since 2022, MPXV has posed a significant threat to global public health. The emergence of thousands of cases across the Western Hemisphere prompted the World Health Organization to declare an emergency. The extensive coevolutionary history of poxviruses with humans has enabled these viruses to develop sophisticated mechanisms to counter the human immune system. Specifically, MPXV employs unique immune evasion strategies against a wide range of immunological elements, presenting a considerable challenge for treatment, especially following the discontinuation of routine smallpox vaccination among the general population. In this review, we start by discussing the entry of the mpox virus and the onset of early infection, followed by an introduction to the mechanisms by which the mpox virus can evade the innate and adaptive immune responses. Two caspase-1 inhibitory proteins and a PKR escape-related protein have been identified as phylogenomic hubs involved in modulating the immune environment during the MPXV infection. With respect to adaptive immunity, mpox viruses exhibit unique and exceptional T-cell inhibition capabilities, thereby comprehensively remodeling the host immune environment. The viral envelope also poses challenges for the neutralizing effects of antibodies and the complement system. The unique immune evasion mechanisms employed by MPXV make novel multi-epitope and nucleic acid-based vaccines highly promising research directions worth investigating. Finally, we briefly discuss the impact of MPXV infection on immunosuppressed patients and the current status of MPXV vaccine development. This review may provide valuable information for the development of new immunological treatments for mpox.
- Immune response
- , Immune evasion
- , Mpox virus (MPXV)
- , Immunopathology
- , DNA sensing

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