Chen Yan, Fachko Devin N, Wu Helen L, Sacha Jonah B, Skalsky Rebecca L
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA.
Oregon National Primate Research Center, Beaverton, OR 97006, USA.
Viruses. 2024 Dec 16;16(12):1923. doi: 10.3390/v16121923.
Lymphocryptoviruses (LCVs) are ubiquitous gamma-herpesviruses that establish life-long infections in both humans and non-human primates (NHPs). In immunocompromised hosts, LCV infections are commonly associated with B cell disorders and malignancies such as lymphoma. In this study, we evaluated simian LCV-encoded small microRNAs (miRNAs) present in lymphoblastoid cell lines (LCLs) derived from a Mauritian cynomolgus macaque () with cyLCV-associated post-transplant lymphoproliferative disease (PTLD) as well as the viral miRNAs expressed in a baboon () LCL that harbors CeHV12. Via sequence comparisons, we further predicted viral miRNAs encoded by LCVs that infect two additional NHP species: stump-tailed macaques () and bonobos (). Together, these species represent two arms of the primate phylogeny: Hominoids () and Old-World monkeys (, ). Through our analysis, we defined sequences for >95 viral miRNAs encoded by these four NHP LCVs. Our study provides the most comprehensive annotation of NHP LCV miRNAs to date, yielding a resource for developing sequence-specific reagents to detect these molecules. Importantly, we further demonstrate that cyLCV miRNAs can be detected in circulation in vivo and have biomarker potential for LCV-related PTLD.
淋巴隐病毒（LCV）是普遍存在的γ-疱疹病毒，可在人类和非人类灵长类动物（NHP）中建立终身感染。在免疫功能低下的宿主中，LCV感染通常与B细胞疾病和淋巴瘤等恶性肿瘤有关。在本研究中，我们评估了从患有环尾猴LCV相关移植后淋巴细胞增生性疾病（PTLD）的毛里求斯食蟹猴（）衍生的淋巴母细胞系（LCL）中存在的猿猴LCV编码的小微小RNA（miRNA），以及在携带CeHV12的狒狒（）LCL中表达的病毒miRNA。通过序列比较，我们进一步预测了感染另外两种NHP物种：短尾猴（）和倭黑猩猩（）的LCV编码的病毒miRNA。这些物种共同代表了灵长类系统发育的两个分支：类人猿（）和旧世界猴（，）。通过我们的分析，我们定义了这四种NHP LCV编码的>95种病毒miRNA的序列。我们的研究提供了迄今为止最全面的NHP LCV miRNA注释，产生了一种用于开发检测这些分子的序列特异性试剂的资源。重要的是，我们进一步证明环尾猴LCV miRNA可以在体内循环中检测到，并且对LCV相关的PTLD具有生物标志物潜力。
