W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Texas A & M University, Department of Entomology, TAMU College Station, Texas, United States of America.
PLoS Biol. 2022 Jun 9;20(6):e3001668. doi: 10.1371/journal.pbio.3001668. eCollection 2022 Jun.
The mosquito's innate immune system defends against a variety of pathogens, and the conserved siRNA pathway plays a central role in the control of viral infections. Here, we show that transgenic overexpression of Dicer2 (Dcr2) or R2d2 resulted in an accumulation of 21-nucleotide viral sequences that was accompanied by a significant suppression of dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) replication, thus indicating the broad-spectrum antiviral response mediated by the siRNA pathway that can be applied for the development of novel arbovirus control strategies. Interestingly, overexpression of Dcr2 or R2d2 regulated the mRNA abundance of a variety of antimicrobial immune genes, pointing to additional functions of DCR2 and R2D2 as well as cross-talk between the siRNA pathway and other immune pathways. Accordingly, transgenic overexpression of Dcr2 or R2d2 resulted in a lesser proliferation of the midgut microbiota and increased resistance to bacterial and fungal infections.
蚊子的先天免疫系统可以抵御多种病原体,而保守的 siRNA 通路在病毒感染的控制中起着核心作用。在这里,我们表明,Dicer2(Dcr2)或 R2d2 的转基因过表达导致 21 个核苷酸的病毒序列积累,伴随着登革热病毒(DENV)、寨卡病毒(ZIKV)和基孔肯雅热病毒(CHIKV)复制的显著抑制,从而表明 siRNA 通路介导的广谱抗病毒反应可用于开发新的虫媒病毒控制策略。有趣的是,Dcr2 或 R2d2 的过表达调节了多种抗菌免疫基因的 mRNA 丰度,这表明 DCR2 和 R2D2 具有额外的功能,以及 siRNA 通路与其他免疫通路之间的串扰。因此,Dcr2 或 R2d2 的转基因过表达导致中肠微生物群的增殖减少,并提高了对细菌和真菌感染的抵抗力。