Fida Kiran, Stanfield Brent A
Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA.
Division of Biotechnology and Molecular Medicine (BioMMed), LSU-SVM, Baton Rouge, Louisiana, USA.
mSystems. 2025 Aug 19;10(8):e0020825. doi: 10.1128/msystems.00208-25. Epub 2025 Jul 23.
A recent article by Torma et al. (G. Torma, Á. Dörmő, Á. Fülöp, D. Tombácz, et al., mSystems 10:e01678-24, 2025, https://doi.org/10.1128/msystems.01678-24) presents the first high-resolution, long-read transcriptomic atlas of Caviid gammaherpesvirus 1 (CaGHV-1), offering insights into its transcriptional complexity. Using nanopore direct RNA and cDNA sequencing, the study maps transcription start sites, polyadenylation signals, alternative splicing, and upstream open reading frames (uORFs), revealing a landscape of coding and non-coding RNAs with pervasive transcriptional overlaps. These features underscore the evolutionary conservation of key regulatory mechanisms across gammaherpesviruses, notably replication and transcription activator (RTA)-mediated transcriptional control. By establishing CaGHV-1 as a promising model for Kaposi's sarcoma-associated herpesvirus (KSHV)-related disease, the work sets a foundation for studies of viral gene regulation, immune evasion, and pathogenesis, including bacterial artificial chromosomes (BACs) for genetic manipulation. Here, we discuss the advances in the study as well as how some limitations remain regarding read coverage biases, sequencing errors, and the uncharacterized functions of non-coding RNAs and emphasize the need for validation and functional assays. This study provides a valuable resource for understanding gammaherpesvirus biology and advancing translational research in viral pathogenesis and therapeutic development.
托马等人近期发表的一篇文章（G. 托马、A. 多尔莫、A. 富勒普、D. 通巴茨等人，《mSystems》10:e01678 - 24，2025年，https://doi.org/10.1128/msystems.01678 - 24）展示了豚鼠γ - 疱疹病毒1型（CaGHV - 1）首个高分辨率、长读长转录组图谱，深入揭示了其转录复杂性。该研究利用纳米孔直接RNA和cDNA测序技术，绘制了转录起始位点、多聚腺苷酸化信号、可变剪接以及上游开放阅读框（uORF），揭示了编码和非编码RNA的格局以及广泛存在的转录重叠现象。这些特征突显了γ - 疱疹病毒关键调控机制在进化上的保守性，尤其是复制和转录激活因子（RTA）介导的转录控制。通过将CaGHV - 1确立为卡波西肉瘤相关疱疹病毒（KSHV）相关疾病的一个有前景的模型，这项工作为病毒基因调控、免疫逃逸和发病机制的研究奠定了基础，包括用于基因操作的细菌人工染色体（BAC）。在此，我们讨论了该研究的进展以及在读取覆盖偏差、测序错误以及非编码RNA功能未知等方面仍然存在的一些局限性，并强调了验证和功能测定的必要性。这项研究为理解γ - 疱疹病毒生物学以及推动病毒发病机制和治疗开发的转化研究提供了宝贵资源。
