TLR5-Mediated Reactivation of Quiescent Ranavirus FV3 in Xenopus Peritoneal Macrophages
TLR5-Mediated Reactivation of Quiescent Ranavirus FV3 in Xenopus Peritoneal Macrophages
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TLR5 介导的非洲爪蟾腹膜巨噬细胞中静止蛙病毒 FV3 的再激活
DOI：
10.1128/jvi.00215-21
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发表时间：
2021
影响因子：
5.4
通讯作者：
Robert, Jacques
中科院分区：
文献类型：
--
作者：
Samanta, Mrinal;Yim, Jinyeong;De Jesús Andino, Francisco;Paiola, Matthieu;Robert, Jacques
蛙病毒（Ranaviruses）如蛙病毒3（frog virus 3，FV3）是大的双链DNA（dsDNA）病毒，其引起新出现的感染性疾病，导致世界范围内两栖动物和其他变温脊椎动物的广泛发病率和死亡率。在FV3的宿主中，有些是高度易感的，而另一些是耐药的和无症状的携带者，可以参与传播传染性病毒。迄今为止，与亚临床感染转变为致死性爆发相关的FV3病毒持续存在过程中所涉及的机制仍然未知。对非洲爪蟾的研究表明，在无症状的FV3携带者动物中，热灭活（HK）大肠杆菌刺激诱导的炎症可引起活动性感染复发。由于Toll样受体（TLR）是识别微生物分子模式的关键，我们研究了它们可能参与炎症诱导的FV3再激活。在10种不同的TLR中，在FV 3感染和HK E. coli刺激后，只有识别细菌产物的TLR5和TLR22表现出差异表达，并且只有TLR5配体鞭毛蛋白能够类似于HK E诱导FV 3再活化。杆菌此外，在体外和体内，只有TLR5配体鞭毛蛋白才能诱导腹腔巨噬细胞中FV3的再激活。这些数据表明TLR5信号通路可以触发FV3再激活，并表明继发性细菌感染或微生物组改变的作用（压力或污染）在两栖动物种群中引发突然的致命疾病爆发，可检测到持续的无症状蛙病毒。重要信息这项在两栖动物非洲爪蟾中的研究提供了新的证据，证明巨噬细胞在静止状态下蛙病毒持续存在中的关键作用，以及这些病原体重新激活成为致命感染。在由巨噬细胞表达的多种微生物传感器中，我们的数据强调了TLR 5刺激在触发驻留的腹膜巨噬细胞中的静止FV 3的再激活中的优势参与，揭示了持续的蛙病毒感染和细菌共感染的再激活之间的机械联系。这表明继发性细菌感染或微生物组改变（压力或污染）在两栖动物种群中引发突发致命疾病爆发的作用，可检测到持续的无症状蛙病毒。
Ranaviruses such as frog virus 3 (FV3) are large double-stranded DNA (dsDNA) viruses causing emerging infectious diseases leading to extensive morbidity and mortality of amphibians and other ectothermic vertebrates worldwide. Among the hosts of FV3, some are highly susceptible, whereas others are resistant and asymptomatic carriers that can take part in disseminating the infectious virus. To date, the mechanisms involved in the processes of FV3 viral persistence associated with subclinical infection transitioning to lethal outbreaks remain unknown. Investigation in Xenopus laevis has revealed that in asymptomatic FV3 carrier animals, inflammation induced by heat-killed (HK) Escherichia coli stimulation can provoke the relapse of active infection. Since Toll-like receptors (TLRs) are critical for recognizing microbial molecular patterns, we investigated their possible involvement in inflammation-induced FV3 reactivation. Among the 10 different TLRs screened for changes in expression levels following FV3 infection and HK E. coli stimulation, only TLR5 and TLR22, both of which recognize bacterial products, showed differential expression, and only the TLR5 ligand flagellin was able to induce FV3 reactivation similarly to HK E. coli. Furthermore, only the TLR5 ligand flagellin induced FV3 reactivation in peritoneal macrophages bothin vitroandin vivo. These data indicate that the TLR5 signaling pathway can trigger FV3 reactivation and suggest a role of secondary bacterial infections or microbiome alterations (stress or pollution) in initiating sudden deadly disease outbreaks in amphibian populations with detectable persistent asymptomatic ranavirus.IMPORTANCEThis study in the amphibian Xenopus laevis provides new evidence of the critical role of macrophages in the persistence of ranaviruses in a quiescent state as well as in the reactivation of these pathogens into a virulent infection. Among the multiple microbial sensors expressed by macrophages, our data underscore the preponderant involvement of TLR5 stimulation in triggering the reactivation of quiescent FV3 in resident peritoneal macrophages, unveiling a mechanistic connection between the reactivation of persisting ranavirus infection and bacterial coinfection. This suggests a role for secondary bacterial infections or microbiome alterations (stress or pollution) in initiating sudden deadly disease outbreaks in amphibian populations with detectable persistent asymptomatic ranavirus.
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影响因子：
4.8
作者：
Robert, J;Gantress, J;Maniero, GD
通讯作者：
Maniero, GD
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.3390/v3112065
发表时间：
2011-11
期刊：
Viruses
影响因子：
--
作者：
Chen G;Robert J
通讯作者：
Robert J
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影响因子：
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作者：
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