Exosomes originating from infection with the cytoplasmic single-stranded RNA virus Rift Valley fever virus (RVFV) protect recipient cells by inducing RIG-I mediated IFN-B response that leads to activation of autophagy.
Exosomes originating from infection with the cytoplasmic single-stranded RNA virus Rift Valley fever virus (RVFV) protect recipient cells by inducing RIG-I mediated IFN-B response that leads to activation of autophagy.
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DOI：
10.1186/s13578-021-00732-z
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发表时间：
2021-12-25
影响因子：
7.5
通讯作者：
Hakami RM
中科院分区：
文献类型：
--
作者：
Alem F;Olanrewaju AA;Omole S;Hobbs HE;Ahsan N;Matulis G;Brantner CA;Zhou W;Petricoin EF;Liotta LA;Caputi M;Bavari S;Wu Y;Kashanchi F;Hakami RM
尽管已有多项研究证实外切体在病毒感染中的作用，但我们对外切体交换在病毒感染过程中调节免疫反应和影响病毒致病机制的了解还处于起步阶段。尤其是对SARS-CoV-2和裂谷热病毒(RVFV)等细胞质单链RNA病毒知之甚少。我们使用RVFV感染作为细胞质单链RNA病毒的模型来解决这一知识差距。RVFV是一种引起RVF的高致病性病原体，RVF是一种人畜共患病，目前还没有有效的治疗性或批准的人类疫苗。我们在这里展示了从感染RVFV的细胞中释放的外切体(命名为Exi-RVFV)对宿主起到保护作用，并为这些影响提供了一个机制模型。我们的结果表明，用EXi-RVFV处理幼稚免疫细胞(U937单核细胞)和幼稚非免疫细胞(HSAECs)都能诱导强烈的RIG-I依赖的干扰素-B激活。我们还证明，这种强烈的抗病毒反应导致处理细胞中自噬的激活，并与对后续病毒感染的抵抗力相关。由于我们已经证明病毒RNA基因组与EXi-RVFV相关，RIG-I的激活可能是通过包装的病毒RNA序列的存在而介导的。使用RVFV感染作为细胞质单链RNA病毒的模型，我们的结果显示了一种新的宿主保护机制，即从感染细胞释放的外糖体(EXi)激活RIG-I，在包括单核细胞在内的幼稚受体细胞中诱导依赖于干扰素的自噬激活。由于单核细胞是RVFV复制的储存库，这种EXi-RVFV诱导的单核细胞自噬激活可能会减缓或阻止病毒在受感染生物体中的传播。这些发现提供了新的机制见解，可能有助于未来有效疫苗或治疗方法的开发，并可能适用于更好地从分子上理解外切体释放如何调节对其他细胞质单链RNA病毒的先天性免疫反应。网上版载有补充材料，可在10.1186/s13578-021-00732-z查阅。
Although multiple studies have demonstrated a role for exosomes during virus infections, our understanding of the mechanisms by which exosome exchange regulates immune response during viral infections and affects viral pathogenesis is still in its infancy. In particular, very little is known for cytoplasmic single-stranded RNA viruses such as SARS-CoV-2 and Rift Valley fever virus (RVFV). We have used RVFV infection as a model for cytoplasmic single-stranded RNA viruses to address this gap in knowledge. RVFV is a highly pathogenic agent that causes RVF, a zoonotic disease for which no effective therapeutic or approved human vaccine exist. We show here that exosomes released from cells infected with RVFV (designated as EXi-RVFV) serve a protective role for the host and provide a mechanistic model for these effects. Our results show that treatment of both naïve immune cells (U937 monocytes) and naïve non-immune cells (HSAECs) with EXi-RVFV induces a strong RIG-I dependent activation of IFN-B. We also demonstrate that this strong anti-viral response leads to activation of autophagy in treated cells and correlates with resistance to subsequent viral infection. Since we have shown that viral RNA genome is associated with EXi-RVFV, RIG-I activation might be mediated by the presence of packaged viral RNA sequences. Using RVFV infection as a model for cytoplasmic single-stranded RNA viruses, our results show a novel mechanism of host protection by exosomes released from infected cells (EXi) whereby the EXi activate RIG-I to induce IFN-dependent activation of autophagy in naïve recipient cells including monocytes. Because monocytes serve as reservoirs for RVFV replication, this EXi-RVFV-induced activation of autophagy in monocytes may work to slow down or halt viral dissemination in the infected organism. These findings offer novel mechanistic insights that may aid in future development of effective vaccines or therapeutics, and that may be applicable for a better molecular understanding of how exosome release regulates innate immune response to other cytoplasmic single-stranded RNA viruses. The online version contains supplementary material available at 10.1186/s13578-021-00732-z.
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影响因子：
7.5
作者：
Gupta S;Rawat S;Arora V;Kottarath SK;Dinda AK;Vaishnav PK;Nayak B;Mohanty S
通讯作者：
Mohanty S
危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
DOI：
10.3390/v3050493
发表时间：
2011-05
期刊：
Viruses
影响因子：
--
作者：
Ikegami T;Makino S
通讯作者：
Makino S
影响因子：
3.7
作者：
Carnec, Xavier;Ermonval, Myriam;Bouloy, Michele
通讯作者：
Bouloy, Michele
影响因子：
3.1
作者：
Colino, Jesus;Snapper, Clifford M.
通讯作者：
Snapper, Clifford M.