Reduced protein-coding transcript diversity in severe dengue emphasises the role of alternative splicing.

IF 3.3 2区 生物学 Q1 BIOLOGY
Life Science Alliance Pub Date : 2024-06-03 Print Date: 2024-08-01 DOI:10.26508/lsa.202402683
Priyanka Mehta, Chinky Shiu Chen Liu, Sristi Sinha, Ramakant Mohite, Smriti Arora, Partha Chattopadhyay, Sandeep Budhiraja, Bansidhar Tarai, Rajesh Pandey
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引用次数: 0

Abstract

Dengue fever, a neglected tropical arboviral disease, has emerged as a global health concern in the past decade. Necessitating a nuanced comprehension of the intricate dynamics of host-virus interactions influencing disease severity, we analysed transcriptomic patterns using bulk RNA-seq from 112 age- and gender-matched NS1 antigen-confirmed hospital-admitted dengue patients with varying severity. Severe cases exhibited reduced platelet count, increased lymphocytosis, and neutropenia, indicating a dysregulated immune response. Using bulk RNA-seq, our analysis revealed a minimal overlap between the differentially expressed gene and transcript isoform, with a distinct expression pattern across the disease severity. Severe patients showed enrichment in retained intron and nonsense-mediated decay transcript biotypes, suggesting altered splicing efficiency. Furthermore, an up-regulated programmed cell death, a haemolytic response, and an impaired interferon and antiviral response at the transcript level were observed. We also identified the potential involvement of the RBM39 gene among others in the innate immune response during dengue viral pathogenesis, warranting further investigation. These findings provide valuable insights into potential therapeutic targets, underscoring the importance of exploring transcriptomic landscapes between different disease sub-phenotypes in infectious diseases.

严重登革热病中蛋白质编码转录本多样性的降低强调了替代剪接的作用。
登革热是一种被忽视的热带虫媒病毒疾病,在过去十年中已成为全球关注的健康问题。为了深入了解宿主与病毒之间影响疾病严重程度的复杂相互作用,我们利用批量 RNA-seq 分析了 112 名年龄和性别匹配、经 NS1 抗原确诊的入院登革热病人的转录组模式,这些病人的病情严重程度各不相同。重症病例表现出血小板计数减少、淋巴细胞增多和中性粒细胞减少,表明免疫反应失调。通过大量 RNA-seq 分析,我们发现差异表达基因与转录本同工酶之间的重叠极少,不同病情严重程度的患者有不同的表达模式。重症患者表现出保留内含子和无义介导衰变转录本生物型的富集,这表明剪接效率发生了改变。此外,在转录本水平上还观察到细胞程序性死亡上调、溶血反应以及干扰素和抗病毒反应受损。我们还发现 RBM39 基因等可能参与了登革热病毒发病过程中的先天性免疫反应,这值得进一步研究。这些发现为潜在的治疗目标提供了宝贵的见解,强调了探索传染病不同疾病亚型之间转录组景观的重要性。
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来源期刊
Life Science Alliance
Life Science Alliance Agricultural and Biological Sciences-Plant Science
CiteScore
5.80
自引率
2.30%
发文量
241
审稿时长
10 weeks
期刊介绍: Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.
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