Abstract：
Host-microbe interactions influence intestinal stem cell (ISC) activity to modulate epithelial turnover and composition. Here, we investigated the functional impacts of viral infection on intestinal homeostasis and the mechanisms by which viral infection alters ISC activity. We report that Drosophila A virus (DAV) infection disrupts intestinal homeostasis in Drosophila by inducing sustained ISC proliferation, resulting in intestinal dysplasia, loss of gut barrier function, and reduced lifespan. We found that additional viruses common in laboratory-reared Drosophila also promote ISC proliferation. The mechanism of DAV-induced ISC proliferation involves progenitor-autonomous epidermal growth factor receptor (EGFR) signaling, c-Jun N-terminal kinase (JNK) activity in enterocytes, and requires Sting-dependent nuclear factor κB (NF-κB) (Relish) activity. We further demonstrate that activating Sting-Relish signaling is sufficient to induce ISC proliferation, promote intestinal dysplasia, and reduce lifespan in the absence of infection. Our results reveal that viral infection can significantly disrupt intestinal physiology, highlight a novel role for Sting-Relish signaling, and support a role for viral infection in aging.
摘要：
宿主-微生物相互作用影响肠干细胞(ISC)活性以调节上皮更新和组成。这里,我们研究了病毒感染对肠道稳态的功能影响,以及病毒感染改变ISC活性的机制.我们报道果蝇A病毒（DAV）感染通过诱导持续的ISC增殖来破坏果蝇的肠道稳态，导致肠道发育不良，肠道屏障功能的丧失，减少寿命。我们发现实验室饲养的果蝇中常见的其他病毒也促进ISC增殖。DAV诱导的ISC增殖的机制涉及祖细胞自主表皮生长因子受体（EGFR）信号，肠上皮细胞c-Jun氨基末端激酶（JNK）活性，并且需要Sting依赖性核因子κB（NF-κB）（Relish）活性。我们进一步证明激活Sting-Relish信号足以诱导ISC增殖，促进肠道发育不良，在没有感染的情况下缩短寿命。我们的结果表明，病毒感染可以显著破坏肠道生理，突出了Sting-Relish信号的一个新角色，并支持病毒感染在衰老中的作用。
