The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity.
The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity.
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DOI：
10.1371/journal.ppat.1011224
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发表时间：
2023-03
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
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蚊子将登革热病毒传播给人类，首先是叮咬部位的皮肤常驻细胞感染。人们对识别蚊子唾液中的传播促进因子以抵消它们非常感兴趣。在这里，我们报告了在感染登革病毒2型的蚊子唾液中发现了高水平的抗免疫亚基因组黄病毒RNA(SfRNA)。我们用三种不同的方法证实唾液中存在sfRNA：Northern印迹、RT-qPCR和RNA测序。接下来，我们展示了唾液sfRNA在洗涤剂敏感的隔间，可能是细胞外小泡中受到保护。为了支持这一假设，我们在蚊子唾液中的囊泡中可视化了病毒RNA，并注意到来自3‘UTR序列的信号显著丰富，这与sfRNA的存在是一致的。此外，我们还发现，与含有更高sfRNA水平的蚊子唾液孵育会导致人类肝癌细胞系和人类原代皮肤成纤维细胞中更高的病毒感染性。在DENV2感染前转染3‘UTRRNA可抑制I型和III型干扰素的诱导和信号转导，并促进病毒复制。因此，我们推测唾液细胞外小泡中存在的sfRNA被传递到咬合处的细胞中，以抑制先天免疫并增强登革热病毒的传播。蚊子传播许多病毒，比如那些引起登革热的病毒，当蚊子叮咬我们时，它们会将唾液沉积在我们的皮肤上，从而将它们带入我们的身体。研究蚊子唾液的叮咬行为和特性的科学家得出结论，唾液中可能含有促进病毒感染的成分。在这项研究中，我们发现当登革热病毒感染蚊子时，人们可以在蚊子的唾液中发现不仅预期的登革热病毒，而且还有一种登革热病毒产品，可以降低我们的抗病毒防御系统。碰巧的是，这种产物被称为非编码RNA，这是一类最近被证明参与重要生物调节的分子。我们认为，通过在被登革热感染的唾液的叮咬部位引入这种RNA，为有效的感染铺平了道路，并使病毒在它与我们的免疫防御之间的第一场战斗中具有优势。
Mosquito transmission of dengue viruses to humans starts with infection of skin resident cells at the biting site. There is great interest in identifying transmission-enhancing factors in mosquito saliva in order to counteract them. Here we report the discovery of high levels of the anti-immune subgenomic flaviviral RNA (sfRNA) in dengue virus 2-infected mosquito saliva. We established that sfRNA is present in saliva using three different methods: northern blot, RT-qPCR and RNA sequencing. We next show that salivary sfRNA is protected in detergent-sensitive compartments, likely extracellular vesicles. In support of this hypothesis, we visualized viral RNAs in vesicles in mosquito saliva and noted a marked enrichment of signal from 3’UTR sequences, which is consistent with the presence of sfRNA. Furthermore, we show that incubation with mosquito saliva containing higher sfRNA levels results in higher virus infectivity in a human hepatoma cell line and human primary dermal fibroblasts. Transfection of 3’UTR RNA prior to DENV2 infection inhibited type I and III interferon induction and signaling, and enhanced viral replication. Therefore, we posit that sfRNA present in salivary extracellular vesicles is delivered to cells at the biting site to inhibit innate immunity and enhance dengue virus transmission. Mosquitoes transmit many viruses, such as those that cause dengue, introducing them in our bodies with the saliva that is deposited in our skins when they bite us. Scientists who study biting behavior and properties of mosquito saliva have concluded that there may be components in saliva that promote virus infection. In this study we show that when dengue virus infects mosquitoes one can find in their saliva not only the expected dengue viruses but also a dengue virus product that can reduce our anti-virus defense systems. It happens that this product is what is known as a non-coding RNA, a class of molecules that have recently been shown to mediate important biological regulation. We propose that by introducing this RNA at the biting site dengue infected saliva prepares the terrain for an efficient infection and gives the virus an advantage in the first battle between it and our immune defenses.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1126/science.aar4142
发表时间：
2018-06-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cai Q;Qiao L;Wang M;He B;Lin FM;Palmquist J;Huang SD;Jin H
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Jin H
影响因子：
48
作者：
Nguyen HQ;Chattoraj S;Castillo D;Nguyen SC;Nir G;Lioutas A;Hershberg EA;Martins NMC;Reginato PL;Hannan M;Beliveau BJ;Church GM;Daugharthy ER;Marti-Renom MA;Wu CT
通讯作者：
Wu CT
影响因子：
3.7
作者：
Lok SM;Costin JM;Hrobowski YM;Hoffmann AR;Rowe DK;Kukkaro P;Holdaway H;Chipman P;Fontaine KA;Holbrook MR;Garry RF;Kostyuchenko V;Wimley WC;Isern S;Rossmann MG;Michael SF
通讯作者：
Michael SF
DOI：
10.1073/pnas.1714530115
发表时间：
2018-03-06
影响因子：
11.1
作者：
Beliveau BJ;Kishi JY;Nir G;Sasaki HM;Saka SK;Nguyen SC;Wu CT;Yin P
通讯作者：
Yin P