AbstractRift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen. Its RNA genome consists of two negative-sense segments (L and M) with one gene each, and one ambisense segment (S) with two opposing genes separated by the noncoding “intergenic region” (IGR). These vRNAs and the complementary cRNAs are encapsidated by nucleoprotein (N).

摘要裂谷热病毒（RVFV）是一种蚊子传播的人畜共患病原体。其RNA基因组由两个负义片段（L和M）组成，每个片段有一个基因，一个双义片段（S）有两个相反的基因，由非编码“基因间区域”（IGR）隔开。这些vRNA和互补cRNA被核蛋白（N）包裹。

Using iCLIP2 (individual-nucleotide resolution UV crosslinking and immunoprecipitation) to map all N-vRNA and N-cRNA interactions, we detect N coverage along the L and M segments. However, the S segment vRNA and cRNA each contain approximately 100 non-encapsidated nucleotides stretching from the IGR into the 5’-adjacent reading frame.

使用iCLIP2（单个核苷酸分辨率UV交联和免疫沉淀）绘制所有N-vRNA和N-cRNA相互作用图，我们检测了L和M段的N覆盖率。然而，S段vRNA和cRNA各自含有大约100个从IGR延伸到5'-相邻阅读框的非包封核苷酸。

These exposed regions are RNase-sensitive and predicted to form stem-loop structures with the mRNA transcription termination motif positioned near the top. Moreover, optimal S segment transcription and replication requires the entire exposed region rather than only the IGR. Thus, the RVFV S segment contains a central, non-encapsidated RNA region with a functional role..

这些暴露的区域对RNase敏感，预计会形成茎环结构，mRNA转录终止基序位于顶部附近。此外，最佳的S段转录和复制需要整个暴露区域，而不仅仅是IGR。因此，RVFV S片段包含一个具有功能作用的中央非包裹RNA区域。。

IntroductionRift Valley fever virus (RVFV; genus Phlebovirus, family Phenuiviridae, order Bunyavirales) is a mosquito-borne zoonotic pathogen endemic in Africa. RVFV regularly causes small outbreaks, but occasionally also major and devastating epidemics leading to the death of thousands of cattle or sheep, and hundreds of humans1.

简介裂谷热病毒（RVFV；Phenuiviridae科Phenuiviridae属Bunyavirales）是一种蚊子传播的人畜共患病原体，在非洲流行。裂谷热病毒经常引起小规模疫情，但偶尔也会引起重大和毁灭性的流行病，导致数千头牛或羊以及数百人死亡1。

Infection of humans usually results in a self-limiting febrile illness, but 1–2% can develop severe symptoms like hemorrhagic fever, encephalitis, or retinitis with case fatality rates of up to 70% among hospitalized patients1,2,3,4.RVFV particles contain mostly negative-stranded genomic RNA (vRNA) that is divided into three segments termed L, M, and S (Fig. 1A).

人类感染通常会导致自限性发热性疾病，但1-2%的患者会出现严重症状，如出血热，脑炎或视网膜炎，住院患者的病死率高达70%1,2,3,4.RVFV颗粒大多含有负链基因组RNA（vRNA），分为三个部分，称为L，M和S（图1A）。

The vRNAs encode the RNA-dependent RNA polymerase (RdRP; L segment), the envelope polyprotein M (M segment), and the N (nucleocapsid) protein (S segment). Upon cell infection, the vRNA segments are individually transcribed into mRNAs (primary transcription), subsequently replicated into antigenomes (cRNAs), and the cRNAs are then replicated back into vRNAs.

vRNA编码RNA依赖性RNA聚合酶（RdRP；L段），包膜多蛋白M（M段）和N（核衣壳）蛋白（S段）。在细胞感染后，将vRNA片段单独转录成mRNA（初级转录），随后复制成抗基因组（cRNA），然后将cRNA复制回vRNA。

The promoters for transcription and replication are formed by the partially complementary sequences at the noncoding 5′ and 3′ ends of each segment, the so-called panhandle5,6.Fig. 1: RVFV particle structure, coding strategy, and iCLIP2 overview.A Schematic representation of a Rift Valley fever virus (RVFV) particle containing the L, M, and S segments’ nucleocapsids.

转录和复制的启动子由每个片段的非编码5'和3'端的部分互补序列形成，即所谓的panhandle5、6。图1:RVFV颗粒结构，编码策略和iCLIP2概述。含有L，M和S片段核衣壳的裂谷热病毒（RVFV）颗粒的示意图。

Each RNA is encapsidated by the N protein (green) and associated with the L polymerase (gray). B Simplified representation of the coding strategy of the RVFV segments. The L and M segments are negative-sense (viral RNA; vRNA) and the S segment employs an ambisense coding strategy (vRNA and complementary RNA; cRNA).

每个RNA被N蛋白（绿色）包裹并与L聚合酶（灰色）相关。B RVFV片段编码策略的简化表示。。

For each segment, coding (dark gray) and non-coding (l.

对于每个片段，编码（深灰色）和非编码（l）。

Data availability

数据可用性

The iCLIP2 read data generated in this study have been deposited in the GEO database under accession numbers ERP153262 (complete study), ERR12252313 (RNAseq rep1), ERR12252314 (RNAseq rep2), ERR12252315 (RNAseq rep3), ERR12252873 (iCLIP virions), ERR12252875 (iCLIP MP-12/BHK), ERR12253852 (iCLIP clone13/BHK).

本研究中产生的iCLIP2读取数据已保存在GEO数据库中，登录号为ERP153262（完整研究），ERR12252313（RNAseq rep1），ERR12252314（RNAseq rep2），ERR12252315（RNAseq rep3），ERR12252873（iCLIP病毒粒子），ERR12252875（iCLIP MP-12/BHK），ERR12253852（iCLIP克隆13/BHK）。

Viral sequences were downloaded from Genbank entries DQ380154.1 (S segment RVFV MP-12), DQ380208.1 (M segment RVFV MP-12); DQ375404.1 (L segment RVFV MP-12), DQ380182.1; (S segment RVFV Clone 13), DQ380213.1 (M segment RVFV Clone 13), DQ375417.1 (L segment RVFV Clone 13). Source data are provided with this paper..

病毒序列从Genbank条目DQ380154.1（S段RVFV MP-12），DQ380208.1（M段RVFV MP-12）下载；DQ375404.1（L段RVFV MP-12），DQ380182.1；（S段RVFV克隆13），DQ380213.1（M段RVFV克隆13），DQ375417.1（L段RVFV克隆13）。本文提供了源数据。。

ReferencesMcMillen, C. M. & Hartman A. L. Rift Valley fever: a threat to pregnant women hiding in plain sight? J. Virol. 95, e01394-19 (2021).Boshra, H., Lorenzo, G., Busquets, N. & Brun, A. Rift Valley fever: recent insights into pathogenesis and prevention. J. Virol. 85, 6098–6105 (2011).PubMed

参考文献McMillen，C.M.&Hartman A.L.裂谷热：对藏在显眼处的孕妇的威胁？J、 维罗尔。95，e01394-19（2021）。Boshra，H.，Lorenzo，G.，Busquets，N。＆Brun，A。裂谷热：对发病机制和预防的最新见解。J、 维罗尔。856098-6105（2011）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ikegami, T. & Makino, S. The pathogenesis of Rift Valley fever. Viruses 3, 493–519 (2011).PubMed

Ikegami，T。＆Makino，S。裂谷热的发病机制。病毒3493-519（2011）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wright, D., Kortekaas, J., Bowden, T. A. & Warimwe, G. M. Rift Valley fever: biology and epidemiology. J. Gen. Virol. 100, 1187–1199 (2019).PubMed

Wright，D.，Kortekaas，J.，Bowden，T.A。和Warimwe，G.M。裂谷热：生物学和流行病学。J、 维罗尔将军。1001187-1199（2019）。PubMed出版社

Google Scholar

谷歌学者

Ferron, F., Weber, F., de la Torre, J. C. & Reguera, J. Transcription and replication mechanisms of Bunyaviridae and Arenaviridae L proteins. Virus Res. 234, 118–134 (2017).PubMed

Ferron，F.，Weber，F.，de la Torre，J.C。＆Reguera，J。布尼亚病毒科和沙粒病毒科L蛋白的转录和复制机制。Virus Res.234118-134（2017）。PubMed出版社

Google Scholar

谷歌学者

Sabsay, K. R. & Te Velthuis, A. J. W. Negative and ambisense RNA virus ribonucleocapsids: more than protective armor. Microbiol. Mol. Biol. Rev. 87, e00082-23 (2023).Kiening, M., Weber, F. & Frishman, D. Conserved RNA structures in the intergenic regions of ambisense viruses. Sci. Rep.

Sabsay，K.R。＆Te Velthuis，A.J.W。阴性和双义RNA病毒核糖核衣壳：不仅仅是保护性装甲。微生物。分子生物学。第87版，e00082-23（2023）。Kiening，M.，Weber，F。＆Frishman，D。在双义病毒的基因间区域中保守RNA结构。科学。代表。

7, 16625 (2017).ADS .

716625（2017）。广告。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Albarino, C. G., Bird, B. H. & Nichol, S. T. A shared transcription termination signal on negative and ambisense RNA genome segments of Rift Valley fever, sandfly fever Sicilian, and Toscana viruses. J. Virol. 81, 5246–5256 (2007).PubMed

Albarino，C.G.，Bird，B.H。＆Nichol，S.T。在裂谷热，西西里沙蝇热和托斯卡纳病毒的阴性和双义RNA基因组片段上共享转录终止信号。J、 维罗尔。815246-5256（2007）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ferron, F. et al. The hexamer structure of the Rift Valley fever virus nucleoprotein suggests a mechanism for its assembly into ribonucleoprotein complexes. PLoS Pathog. 7, e1002030 (2011).Hopkins, F. R. et al. The native orthobunyavirus ribonucleoprotein possesses a helical architecture.

裂谷热病毒核蛋白的六聚体结构表明其组装成核糖核蛋白复合物的机制。PLoS Pathog。7，e1002030（2011）。霍普金斯（Hopkins），F.R。等人。天然正丁烷病毒核糖核蛋白具有螺旋结构。

mBio 13, e0140522 (2022).PubMed .

mBio 13，e0140522（2022）。PubMed。

Google Scholar

谷歌学者

Luo M., Terrell J. R. & McManus S. A. Nucleocapsid structure of negative strand RNA virus. Viruses 12, 835 (2020).Olal, D. et al. Structural insights into RNA encapsidation and helical assembly of the Toscana virus nucleoprotein. Nucleic Acids Res. 42, 6025–6037 (2014).PubMed

Luo M.，Terrell J.R。＆McManus S.A。负链RNA病毒的核衣壳结构。病毒12835（2020）。Olal，D。等人。Toscana病毒核蛋白的RNA包被和螺旋组装的结构见解。核酸研究426025-6037（2014）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Raymond, D. D., Piper, M. E., Gerrard, S. R. & Smith, J. L. Structure of the Rift Valley fever virus nucleocapsid protein reveals another architecture for RNA encapsidation. Proc. Natl Acad. Sci. USA 107, 11769–11774 (2010).ADS

Raymond，D.D.，Piper，M.E.，Gerrard，S.R。＆Smith，J.L。裂谷热病毒核衣壳蛋白的结构揭示了RNA包被的另一种结构。程序。国家科学院。科学。美国10711769-11774（2010）。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Raymond, D. D., Piper, M. E., Gerrard, S. R., Skiniotis, G. & Smith, J. L. Phleboviruses encapsidate their genomes by sequestering RNA bases. Proc. Natl Acad. Sci. USA 109, 19208–19213 (2012).ADS

Raymond，D.D.，Piper，M.E.，Gerrard，S.R.，Skiniotis，G。＆Smith，J.L。静脉病毒通过隔离RNA碱基包裹其基因组。程序。国家科学院。科学。美国10919208-19213（2012）。广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lee, N. et al. Genome-wide analysis of influenza viral RNA and nucleoprotein association. Nucleic Acids Res. 45, 8968–8977 (2017).PubMed

Lee，N.等人。流感病毒RNA和核蛋白关联的全基因组分析。核酸研究458968-8977（2017）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Williams, G. D. et al. Nucleotide resolution mapping of influenza A virus nucleoprotein-RNA interactions reveals RNA features required for replication. Nat. Commun. 9, 465 (2018).ADS

Williams，G.D.等人。甲型流感病毒核蛋白-RNA相互作用的核苷酸分辨率图谱揭示了复制所需的RNA特征。国家公社。9465（2018）。广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Dadonaite, B. et al. The structure of the influenza A virus genome. Nat. Microbiol. 4, 1781–1789 (2019).PubMed

Dadonaite，B。等人。甲型流感病毒基因组的结构。自然微生物。41781-1789（2019）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Mirska, B. et al. In vivo secondary structural analysis of Influenza A virus genomic RNA. Cell Mol. Life Sci. 80, 136 (2023).PubMed

Mirska，B。等人。甲型流感病毒基因组RNA的体内二级结构分析。细胞分子生命科学。80136（2023）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Klumpp, K., Ruigrok, R. W. & Baudin, F. Roles of the influenza virus polymerase and nucleoprotein in forming a functional RNP structure. EMBO J. 16, 1248–1257 (1997).PubMed

Klumpp，K.，Ruigrok，R。W。和Baudin，F。流感病毒聚合酶和核蛋白在形成功能性RNP结构中的作用。EMBO J.161248–1257（1997）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Buchbender, A. et al. Improved library preparation with the new iCLIP2 protocol. Methods 178, 33–48 (2020).PubMed

Buchbender，A。等人用新的iCLIP2方案改进了文库制备。方法178,33-48（2020）。PubMed出版社

Google Scholar

谷歌学者

Konig, J. et al. iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat. Struct. Mol. Biol. 17, 909–915 (2010).PubMed

Konig，J。等人，iCLIP揭示了hnRNP颗粒在单个核苷酸分辨率下剪接的功能。自然结构。分子生物学。17909-915（2010）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Haberman, N. et al. Insights into the design and interpretation of iCLIP experiments. Genome Biol. 18, 7 (2017).PubMed

Haberman，N.等人对iCLIP实验的设计和解释的见解。基因组生物学。。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gunzl, A., Palfi, Z. & Bindereif, A. Analysis of RNA-protein complexes by oligonucleotide-targeted RNase H digestion. Methods 26, 162–169 (2002).PubMed

Gunzl，A.，Palfi，Z。＆Bindereif，A。通过寡核苷酸靶向RNase H消化分析RNA-蛋白质复合物。方法26162-169（2002）。PubMed出版社

Google Scholar

谷歌学者

Muller, R. et al. Characterization of clone 13, a naturally attenuated avirulent isolate of Rift Valley fever virus, which is altered in the small segment. Am. J. Trop. Med. Hyg. 53, 405–411 (1995).PubMed

Muller，R.等人。克隆13的表征，克隆13是裂谷热病毒的自然减毒无毒分离株，在小片段中发生了改变。Am.J.Trop。医学保健。。PubMed出版社

Google Scholar

谷歌学者

Billecocq, A. et al. NSs protein of Rift Valley fever virus blocks interferon production by inhibiting host gene transcription. J. Virol. 78, 9798–9806 (2004).PubMed

Billecocq，A。等人。裂谷热病毒的NSs蛋白通过抑制宿主基因转录来阻断干扰素的产生。J、 维罗尔。789798-9806（2004）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Vialat, P., Billecocq, A., Kohl, A. & Bouloy, M. The S segment of Rift Valley fever phlebovirus (Bunyaviridae) carries determinants for attenuation and virulence in mice. J. Virol. 74, 1538–1543 (2000).PubMed

Vialat，P.，Billecocq，A.，Kohl，A。＆Bouloy，M。裂谷热静脉病毒（布尼亚病毒科）的S段携带小鼠减毒和毒力的决定因素。J、 维罗尔。741538-1543（2000）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ikegami, T., Won, S., Peters, C. J. & Makino, S. Characterization of Rift Valley fever virus transcriptional terminations. J. Virol. 81, 8421–8438 (2007).PubMed

Ikegami，T.，Won，S.，Peters，C.J。＆Makino，S。裂谷热病毒转录终止的表征。J、 维罗尔。818421-8438（2007）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lara, E., Billecocq, A., Leger, P. & Bouloy, M. Characterization of wild-type and alternate transcription termination signals in the Rift Valley fever virus genome. J. Virol. 85, 12134–12145 (2011).PubMed

Lara，E.，Billecocq，A.，Leger，P。＆Bouloy，M。表征裂谷热病毒基因组中的野生型和替代转录终止信号。J、 维罗尔。8512134-12145（2011）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Habjan, M., Penski, N., Spiegel, M. & Weber, F. T7 RNA polymerase-dependent and -independent systems for cDNA-based rescue of Rift Valley fever virus. J. Gen. Virol. 89, 2157–2166 (2008).PubMed

。J、 维罗尔将军。892157-2166（2008）。PubMed出版社

Google Scholar

谷歌学者

Habjan, M. et al. Efficient production of Rift Valley fever virus-like particles: the antiviral protein MxA can inhibit primary transcription of bunyaviruses. Virology 385, 400–408 (2009).PubMed

Habjan，M.等人。有效产生裂谷热病毒样颗粒：抗病毒蛋白MxA可以抑制布尼亚病毒的初级转录。。PubMed出版社

Google Scholar

谷歌学者

Klemm, C. et al. Systems to establish bunyavirus genome replication in the absence of transcription. J. Virol. 87, 8205–8212 (2013).PubMed

Klemm，C.等人在没有转录的情况下建立布尼亚病毒基因组复制的系统。J、 维罗尔。878205-8212（2013）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kuri, T., Habjan, M., Penski, N. & Weber, F. Species-independent bioassay for sensitive quantification of antiviral type I interferons. Virol. J. 7, 50 (2010).PubMed

Kuri，T.，Habjan，M.，Penski，N。＆Weber，F。用于敏感定量抗病毒I型干扰素的物种独立生物测定。维罗尔。J、 7，50（2010）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Malet, H., Williams, H. M., Cusack, S. & Rosenthal, M. The mechanism of genome replication and transcription in bunyaviruses. PLoS Pathog. 19, e1011060 (2023).PubMed

Malet，H.，Williams，H.M.，Cusack，S。＆Rosenthal，M。布尼亚病毒基因组复制和转录的机制。PLoS Pathog。19，e1011060（2023）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Barr J. D., Weber F., Schmaljohn C. S. Bunyavirales: the viruses and their replication. In: Fields Virology (ed. Whelan, S.) (Lippincott Williams & Wilkins – Philadelphia, USA, 2020).Moy, R. H. et al. Stem-loop recognition by DDX17 facilitates miRNA processing and antiviral defense. Cell 158, 764–777 (2014).PubMed .

Barr J.D.，Weber F.，Schmaljohn C.S.Bunyavirales：病毒及其复制。在：Fields Virology（ed.Whelan，S.）（Lippincott Williams＆Wilkins–Philadelphia，USA，2020）。通过DDX17识别茎环有助于miRNA加工和抗病毒防御。细胞158764-777（2014）。PubMed。

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Xu, L. et al. Limiting viral replication in hepatocytes alters Rift Valley fever virus disease manifestations. J. Virol. 97, e0085323 (2023).PubMed

Xu，L.等人。限制肝细胞中的病毒复制会改变裂谷热病毒的疾病表现。J、 维罗尔。97，e0085323（2023）。PubMed出版社

Google Scholar

谷歌学者

Sabin, L. R. et al. Dicer-2 processes diverse viral RNA species. PLoS ONE 8, e55458 (2013).ADS

Sabin，L.R。等人Dicer-2处理不同的病毒RNA种类。PLoS ONE 8，e55458（2013）。广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hedil, M., Hassani-Mehraban, A., Lohuis, D. & Kormelink, R. Analysis of the A-U rich hairpin from the intergenic region of tospovirus S RNA as target and inducer of RNA silencing. PLoS ONE 9, e106027 (2014).ADS

Hedil，M.，Hassani-Mehraban，A.，Lohuis，D。＆Kormelink，R。分析来自tospovirus S RNA基因间区域的富含A-U的发夹作为RNA沉默的靶标和诱导物。PLoS ONE 9，e106027（2014）。广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ly, H. J. & Ikegami, T. Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins. Virol. J. 13, 118 (2016).PubMed

Ly，H。J。＆Ikegami，T。裂谷热病毒NSs蛋白的功能以及与其他布尼亚病毒NSs蛋白的相似性。维罗尔。J、 13118（2016）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wuerth, J. D. & Weber F. Phleboviruses and the type I interferon response. Viruses 8, 174 (2016).Bolte, H., Rosu, M. E., Hagelauer, E., Garcia-Sastre, A. & Schwemmle, M. Packaging of the influenza virus genome is governed by a plastic network of RNA- and nucleoprotein-mediated interactions.

Wuerth，J.D。＆Weber F.静脉病毒和I型干扰素反应。病毒8174（2016）。Bolte，H.，Rosu，M.E.，Hagelauer，E.，Garcia-Sastre，A。＆Schwemmle，M。流感病毒基因组的包装由RNA和核蛋白介导的相互作用的塑料网络控制。

J. Virol. 93, e01861-18 (2019).Haralampiev, I. et al. Selective flexible packaging pathways of the segmented genome of influenza A virus. Nat. Commun. 11, 4355 (2020).ADS .

J、 维罗尔。93，e01861-18（2019）。Haralampiev，I。等人。甲型流感病毒分段基因组的选择性软包装途径。国家公社。114355（2020）。广告。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Mallapaty S. The pathogens that could spark the next pandemic. Nature 632, 488 (2024)Alkan, C., Jurado-Cobena, E. & Ikegami, T. Advancements in Rift Valley fever vaccines: a historical overview and prospects for next generation candidates. NPJ Vaccines 8, 171 (2023).PubMed

Mallapaty S.可能引发下一次大流行的病原体。Nature 632488（2024）Alkan，C.，Jurado Cobena，E。＆Ikegami，T。裂谷热疫苗的进展：历史概述和下一代候选人的前景。NPJ疫苗8171（2023）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bird, B. H. et al. Rift Valley fever virus vaccine lacking the NSs and NSm genes is safe, nonteratogenic, and confers protection from viremia, pyrexia, and abortion following challenge in adult and pregnant sheep. J. Virol. 85, 12901–12909 (2011).PubMed

Bird，B.H.等人。缺乏NSs和NSm基因的裂谷热病毒疫苗是安全的，非致病性的，并且在成年和怀孕的绵羊受到攻击后可以防止病毒血症，发热和流产。J、 维罗尔。8512901–12909（2011）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gowen, B. B. et al. Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge. Antivir. Res. 98, 135–143 (2013).PubMed

Gowen，B.B.等人。暴露后接种缺乏NSs的MP-12疫苗可保护小鼠免受致命的裂谷热病毒攻击。抗病毒药物。第98135-143号决议（2013年）。PubMed出版社

Google Scholar

谷歌学者

Lihoradova, O. A. et al. Characterization of Rift Valley fever virus MP-12 strain encoding NSs of Punta Toro virus or sandfly fever Sicilian virus. PLoS Negl. Trop. Dis. 7, e2181 (2013).PubMed

Lihoradova，O.A.等人。编码蓬塔托罗病毒或沙蝇热西西里病毒NSs的裂谷热病毒MP-12株的表征。公共科学图书馆。托普。Dis。7，e2181（2013）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Nishiyama, S. et al. Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR. Virulence 7, 871–881 (2016).PubMed

Nishiyama，S.等人。通过编码沙蝇热静脉病毒NSs或显性负性PKR的嵌合S片段减弱致病性裂谷热病毒株。毒力7871-881（2016）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Islam, M. K. et al. High-throughput screening using a whole-cell virus replication reporter gene assay to identify inhibitory compounds against Rift Valley fever virus infection. J. Biomol. Screen 21, 354–362 (2016).PubMed

Islam，M.K.等人。使用全细胞病毒复制报告基因测定进行高通量筛选，以鉴定针对裂谷热病毒感染的抑制性化合物。J、 生物摩尔。屏幕21354-362（2016）。PubMed出版社

Google Scholar

谷歌学者

Habjan, M. et al. NSs protein of Rift Valley fever virus induces the specific degradation of the double-stranded RNA-dependent protein kinase. J. Virol. 83, 4365–4375 (2009).PubMed

Habjan，M。等人。裂谷热病毒的NSs蛋白诱导双链RNA依赖性蛋白激酶的特异性降解。J、 维罗尔。834365-4375（2009）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wuerth, J. D. et al. eIF2B as a target for viral evasion of PKR-mediated translation inhibition. mBio 11, e00976-20 (2020).Shalamova, L., Lorenzo, G., Brun, A., Rossbach, O. & Weber, F. Nucleotide resolution mapping of Rift Valley fever virus nucleoprotein-genome RNA interactions. Methods Mol.

Wuerth，J.D。等人，eIF2B作为病毒逃避PKR介导的翻译抑制的靶标。mBio 11，e00976-20（2020）。Shalamova，L.，Lorenzo，G.，Brun，A.，Rossbach，O。＆Weber，F。裂谷热病毒核蛋白-基因组-RNA相互作用的核苷酸分辨率作图。方法分子。

Biol. 2824, 281–318 (2024).PubMed .

Biol.2824，281–318（2024）。PubMed。

Google Scholar

谷歌学者

Martin-Folgar, R. et al. Development and characterization of monoclonal antibodies against Rift Valley fever virus nucleocapsid protein generated by DNA immunization. MAbs 2, 275–284 (2010).PubMed

Martin Folgar，R.等人。DNA免疫产生的抗裂谷热病毒核衣壳蛋白单克隆抗体的开发和表征。单克隆抗体2275-284（2010）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Van Nostrand, E. L. et al. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nat. Methods 13, 508–514 (2016).PubMed

Van Nostrand，E.L.等人。通过增强CLIP（eCLIP）在转录组范围内发现RNA结合蛋白结合位点。《自然方法》13508-514（2016）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sayers, E. W. et al. Database resources of the National Center for Biotechnology Information in 2023. Nucleic Acids Res. 51, D29–D38 (2023).PubMed

2023年国家生物技术信息中心的数据库资源。核酸研究51，D29-D38（2023）。PubMed出版社

Google Scholar

谷歌学者

Barth, P., Jaenicke S., & Förster, F. patrick-barth/PARANOID: v0.1. In: Zenodo. https://doi.org/10.5281/zenodo.13323413 (2024).Smith, T., Heger, A. & Sudbery, I. UMI-tools: modeling sequencing errors in Unique Molecular Identifiers to improve quantification accuracy. Genome Res. 27, 491–499 (2017).PubMed .

Barth，P.，Jaenicke S.，＆Förster，F。patrick Barth/偏执狂：v0.1。在：Zenodo。https://doi.org/10.5281/zenodo.13323413（2024年）。Smith，T.，Heger，A。＆Sudbery，I。UMI工具：在独特的分子标识符中建模测序错误以提高定量准确性。基因组研究27491-499（2017）。PubMed。

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).PubMed

Langmead，B。＆Salzberg，S.L。与Bowtie 2快速间隙读取对齐。《自然方法》9357-359（2012）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Team RC. R: A Language and Environment for Statistical Computing (Foundation for Statistical Computing, 2020).Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24–26 (2011).PubMed

团队RC。R： 统计计算的语言和环境（统计计算基金会，2020年）。Robinson，J.T.等人，《整合基因组学查看器》。美国国家生物技术公司。29,24-26（2011）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kainulainen, M., Lau, S., Samuel, C. E., Hornung, V. & Weber, F. NSs virulence factor of Rift Valley fever virus engages the F-box proteins FBXW11 and beta-TRCP1 to degrade the antiviral protein kinase PKR. J. Virol. 90, 6140–6147 (2016).PubMed

Kainulainen，M.，Lau，S.，Samuel，C.E.，Hornung，V。＆Weber，F。裂谷热病毒的NSs毒力因子与F-box蛋白FBXW11和β-TRCP1结合以降解抗病毒蛋白激酶PKR。J、 维罗尔。906140-6147（2016）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Janssen, S. & Giegerich, R. The RNA shapes studio. Bioinformatics 31, 423–425 (2015).PubMed

Janssen，S。和Giegerich，R。RNA形状工作室。生物信息学31423-425（2015）。PubMed出版社

Google Scholar

谷歌学者

Johnson, P. Z. & Simon, A. E. RNAcanvas: interactive drawing and exploration of nucleic acid structures. Nucleic Acids Res. 51, W501–W508 (2023).PubMed

Johnson，P.Z。＆Simon，A.E。RNAcanvas：核酸结构的交互式绘图和探索。核酸研究51，W501–W508（2023）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesAcknowledgementsThis work is supported by the Deutsche Forschungsgemeinschaft (DFG) grants SFB 1021 project number 197785619 (F.W., T.H., R.K.H.), GRK2355 project number 325443116 (F.W., L.S., P.B., A.G., O.R.), the Swedish Research Council 2018-05766 (F.W.), the Ministerio de Ciencia e Innovación/Agencia Española de Investigación MCIN/AEI (A.B.), and the Fondo Europeo de Desarrollo Regional (FEDER) by the European Union project PID2021-122567OB-I00 granted by MCIN/AEI /10.13039/501100011033 / FEDER, EU (A.B.).FundingOpen Access funding enabled and organized by Projekt DEAL.Author informationAuthor notesPatrick BarthPresent address: Cell Biology and Plant Biochemistry, University of Regensburg, Regensburg, GermanyKatharina HumpertPresent address: Institute of Molecular Oncology, Genomics Core Facility, Philipps-University, Marburg, GermanyAuthors and AffiliationsInstitute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, Giessen, GermanyLyudmila Shalamova, Matthew J.

下载参考文献致谢这项工作得到了德国科学基金会（DFG）资助的SFB 1021项目编号197785619（F.W.，T.H.，R.K.H.），GRK2355项目编号325443116（F.W.，L.S.，P.B.，A.G.，O.R.），瑞典研究委员会2018-05766（F.W.），创新与创新部长/研究机构（A.B.）和欧洲区域基金会（Fedelo Europeo de Desarrollo Regional）的支持R）由MCIN/AEI/10.13039/501100011033/FEDER，EU（A.B.）授予的欧盟项目PID2021-122567OB-I00。资金开放获取资金由Projekt交易启用和组织。作者信息作者注SPAtrick BarthPresent地址：细胞生物学和植物生物化学，雷根斯堡大学，雷根斯堡，德国Katharina HumpertPresent地址：分子肿瘤学研究所，基因组学核心设施，菲利普大学，马尔堡，德国作者和附属机构病毒学研究所，FB10兽医学，Justus Liebig University，Giessen，GermanyLyudmila Shalamova，Matthew J。

Pickin, Kiriaki Kouti & Friedemann WeberBioinformatics & Systems Biology, Justus-Liebig University, Giessen, GermanyPatrick Barth & Alexander GoesmannInstitute for Medical Microbiology, FB11-Medicine, Justus-Liebig University, Giessen, GermanyBenjamin Ott, Katharina Humpert & Torsten HainAlgorithmic Bioinformatics, Justus-Liebig University, Giessen, GermanyStefan JanssenCentro de Investigación en Sanidad Animal (CISA-INIA/CSIC), Valdeolmos, Madrid, SpainGema Lorenzo & Alejandro BrunInstitute of Pharmaceutical Chemistry, Philipps-University Marburg, Marburg, GermanyRoland K.

。

HartmannInstitute for Biochemistry, FB 08-Biology and Chemistry, Justus-Liebig University, Giessen, GermanyOliver RossbachAuthorsLyudmila ShalamovaView author publicationsYou can also se.

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PubMed Google ScholarContributionsL.S., R.K.H., O.R., and F.W. designed the research. L.S., M.J.P., K.K., B.O., K.H., and O.R. acquired the data. P.B. processed the data. L.S., P.B., M.J.P., K.K., S.J., G.L., A.B., A.G., O.R., and F.W. analyzed and interpreted the data. L.S., A.B., A.G., T.H., R.K.H., O.R., and F.W.

PubMed谷歌学术贡献l。S、 ，R.K.H.，O.R。和F.W.设计了这项研究。五十、 。P、 B.处理数据。五十、 S.，P.B.，M.J.P.，K.K.，S.J.，G.L.，A.B.，A.G.，O.R。和F.W.分析并解释了数据。五十、 S.，A.B.，A.G.，T.H.，R.K.H.，O.R。和F.W。

acquired the funding. L.S. and F.W. wrote the paper. All authors reviewed and approved the final manuscript.Corresponding authorCorrespondence to.

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Reprints and permissionsAbout this articleCite this articleShalamova, L., Barth, P., Pickin, M.J. et al. Nucleocapsids of the Rift Valley fever virus ambisense S segment contain an exposed RNA element in the center that overlaps with the intergenic region.

转载和许可本文引用本文Shalamova，L.，Barth，P.，Pickin，M.J。等人。裂谷热病毒ambisense S片段的核衣壳在与基因间区域重叠的中心含有暴露的RNA元件。

Nat Commun 15, 7602 (2024). https://doi.org/10.1038/s41467-024-52058-2Download citationReceived: 16 October 2023Accepted: 21 August 2024Published: 01 September 2024DOI: https://doi.org/10.1038/s41467-024-52058-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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