Thibeaux Amber, Lu Max Yang, Martin Marshall, Rodwell Michael, Faber Victoria, Sheffield Lakbira, Fierst Janna L, Chtarbanova Stanislava
Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA.
Department of Biological Sciences, Florida International University, Miami, FL, USA.
Virulence. 2025 Dec;16(1):2549497. doi: 10.1080/21505594.2025.2549497. Epub 2025 Aug 25.
MicroRNAs (miRNAs) are small non-coding RNAs ~ 19-22 nt long that post-transcriptionally regulate their mRNA targets. In , the role of miRNAs has mostly been studied in regard to bacterial infection, yielding insights about their regulatory function in innate immunity. However, fewer studies have focused on viral infections, and importantly, how miRNAs modulate aging immune responses is not fully understood. Here, we performed small RNA-sequencing demonstrating that systemic Flock House Virus (FHV) infection of flies leads to differential microRNA expression and that this response differs with aging. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified cellular pathways and biological processes which may be regulated by dynamic expression of microRNAs during infection. For 17 candidate miRNAs, we tested lines with miRNA knockdown for their survival of systemic FHV challenge. In response to infection, among miRNA knockdown lines, females consistently outlived males, and young flies generally outlived their aged counterparts. Furthermore, miRNA knockdown lines generally displayed increased susceptibility to viral infection in comparison to controls, particularly prominent among males. For one miRNA chosen for further study, , its dysregulation resulted in decreased survival independent of changes in viral load, suggesting a role in disease tolerance rather than resistance. Lastly, knockdown of the () gene - a predicted target of - was associated with improved survival of FHV. This work identifies changes in miRNA expression in the aging antiviral response and highlights one miRNA with a role in disease tolerance to FHV in .
微小RNA(miRNA)是长度约为19 - 22个核苷酸的小型非编码RNA,它们在转录后调控其mRNA靶标。在过去的研究中,miRNA的作用主要是在细菌感染方面进行研究,从而深入了解它们在先天免疫中的调节功能。然而,针对病毒感染的研究较少,重要的是,miRNA如何调节衰老免疫反应尚未完全了解。在这里,我们进行了小RNA测序,结果表明果蝇全身性感染鸡瘟病毒(FHV)会导致微小RNA表达差异,并且这种反应会随着衰老而不同。基因本体论和京都基因与基因组百科全书分析确定了在感染过程中可能由微小RNA动态表达调控的细胞途径和生物学过程。对于17个候选miRNA,我们测试了17个miRNA敲低品系在全身性FHV攻击下的存活情况。在应对感染时,在miRNA敲低品系中,雌性果蝇的存活时间始终长于雄性,年轻果蝇通常比年老果蝇存活时间长。此外,与对照组相比,miRNA敲低品系通常对病毒感染的易感性增加,在雄性中尤为明显。对于一个选择进一步研究的miRNA,其失调导致存活率下降,且与病毒载量变化无关,这表明它在疾病耐受性而非抗性中发挥作用。最后,预测为该miRNA靶标的()基因的敲低与FHV存活率的提高有关。这项工作确定了衰老抗病毒反应中miRNA表达的变化,并突出了一个在果蝇对FHV的疾病耐受性中起作用的miRNA。