Sun Haowen, Gu Rongrong, Tang Tingting, Rai Kul Raj, Chen Ji-Long
Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
Int J Mol Sci. 2025 Apr 12;26(8):3651. doi: 10.3390/ijms26083651.
Micropeptides (miPEPs), encoded by short open reading frames (sORFs) within various genomic regions, have recently emerged as critical regulators of multiple biological processes. In particular, these small molecules are now increasingly being recognized for their role in modulating viral replication, pathogenesis, and host immune responses. Both host miPEPs and virus-derived miPEPs have been noted for their ability to regulate virus-host interactions through diversified mechanisms such as altering protein stability and modulating protein-protein interactions. Although thousands of sORFs have been annotated as having the potential to encode miPEPs, only a small number have been experimentally validated so far, with some directly linked to virus-host interactions and a small subset associated with immune modulation, indicating that the investigation of miPEPs is still in its infancy. The systematic identification, translational status assessment, in-depth characterization, and functional analysis of a substantial fraction of sORFs encoding miPEPs remain largely underexplored. Further studies are anticipated to uncover the intricate mechanisms underlying virus-host interactions, host immune modulation, and the broader biological functions of miPEPs. This article will review the emerging roles of miPEPs in virus-host interactions and host immunity, and discuss the challenges and future perspectives of miPEP studies.
微小肽（miPEPs）由各种基因组区域内的短开放阅读框（sORFs）编码，最近已成为多种生物学过程的关键调节因子。特别是，这些小分子现在因其在调节病毒复制、发病机制和宿主免疫反应中的作用而越来越受到认可。宿主miPEPs和病毒衍生的miPEPs都因其能够通过改变蛋白质稳定性和调节蛋白质-蛋白质相互作用等多种机制来调节病毒-宿主相互作用而受到关注。尽管已有数千个sORFs被注释为有可能编码miPEPs，但到目前为止只有少数得到了实验验证，其中一些与病毒-宿主相互作用直接相关，还有一小部分与免疫调节有关，这表明对miPEPs的研究仍处于起步阶段。对相当一部分编码miPEPs的sORFs进行系统鉴定、转化状态评估、深入表征和功能分析在很大程度上仍未得到充分探索。预计进一步的研究将揭示病毒-宿主相互作用、宿主免疫调节以及miPEPs更广泛生物学功能背后的复杂机制。本文将综述miPEPs在病毒-宿主相互作用和宿主免疫中的新作用，并讨论miPEP研究的挑战和未来前景。
