Molecular Biology of Rift Valley Fever Virus

Bouloy, Michèle

doi:10.2174/1874357901004010008

Cited by 66 publications

(89 citation statements)

References 96 publications

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“…Aedes and Culex mosquitoes, can cause encephalitis and hemorrhagic fever (7). Another member of the Bunyavirus family, Crimean-Congo hemorrhagic fever virus, vectored by ticks and causing severe disease in humans (30% mortality), is endemic in many countries in Africa, Europe, and Asia.…”

Section: Rift Valley Fever Virus (Rvf) a Bunyavirus That Is Transmitmentioning

confidence: 99%

RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila

Mueller

Gausson

Vodovar

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

135

134

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Activation of innate antiviral responses in multicellular organisms relies on the recognition of structural differences between viral and cellular RNAs. Double-stranded (ds)RNA, produced during viral replication, is a well-known activator of antiviral defenses and triggers interferon production in vertebrates and RNAi in invertebrates and plants. Previous work in mammalian cells indicates that negative-strand RNA viruses do not appear to generate dsRNA, and that activation of innate immunity is triggered by the recognition of the uncapped 5′ ends of viral RNA. This finding raises the question whether antiviral RNAi, which is triggered by the presence of dsRNA in insects, represents an effective host-defense mechanism against negative-strand RNA viruses. Here, we show that the negative-strand RNA virus vesicular stomatitis virus (VSV) does not produce easily detectable amounts of dsRNA in Drosophila cells. Nevertheless, RNAi represents a potent response to VSV infection, as illustrated by the high susceptibility of RNAi-defective mutant flies to this virus. VSV-derived small RNAs produced in infected cells or flies uniformly cover the viral genome, and equally map the genome and antigenome RNAs, indicating that they derive from dsRNA. Our findings reveal that RNAi is not restricted to the defense against positive-strand or dsRNA viruses but can also be highly efficient against a negative-strand RNA virus. This result is of particular interest in view of the frequent transmission of medically relevant negative-strand RNA viruses to humans by insect vectors.deep sequencing | arbovirus | Dicer-2 | AGO2 | small RNA profiling

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Section: Rift Valley Fever Virus (Rvf) a Bunyavirus That Is Transmitmentioning

confidence: 99%

RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila

Mueller

Gausson

Vodovar

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

135

134

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“…In addition to these viruses, which are transmitted between mammalian hosts, several negative-stranded RNA viruses, called arthropod-borne viruses or arboviruses, are transmitted to humans by insect vectors. For example, Rift Valley Fever virus, a bunyavirus that is transmitted by Aedes and Culex mosquitoes, causes encephalitis and hemorrhagic fever (1). Another member of the family Bunyaviridae, Crimean-Congo hemorrhagic fever virus, which is endemic in many countries of Africa, Europe, and Asia, is transmitted by ticks and causes severe disease in humans, with 30z mortality.…”

Section: Introductionmentioning

confidence: 99%

Argonaute 2 Suppresses Japanese Encephalitis Virus Infection in <i>Aedes aegypti</i>

et al. 2017

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SUMMARY: There are three main innate immune mechanisms against viruses in mosquitoes. Infection with the flavivirus dengue virus is controlled by RNA interference (RNAi) and the JAK-STAT and Toll signaling pathways. This study showed that another flavivirus, Japanese encephalitis virus (JEV), did not invade the salivary glands of Aedes aegypti and that this may be a result of the innate immune resistance to the virus. Argonaute 2 (Ago2) plays a critical role in the RNAi pathway. To understand the mechanism of JEV resistance, we focused on Ago2 as a possible target of JEV. Here, we show that the expression of MyD88 (a mediator of Toll signaling) and Ago2 mRNAs was induced by JEV in the salivary glands of Ae. aegypti mosquitoes and that Ago2, JAK, and domeless (DOME ) mRNAs were induced by JEV in the bodies of Ae. aegypti mosquitoes. Double-stranded (ds) Ago2 RNA enhanced JEV infection, and the virus was detected in salivary glands by immunofluorescence assay. In contrast, MyD88 dsRNA had no effect on JEV infection. These data suggest that Ago2 plays a crucial role in mediating the innate immune response of Ae. aegypti to JEV in a manner similar to that employed by dengue virus.

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“…The particles of RVFV consist of a lipid envelope with two integral glycoproteins, Gn and Gc, surrounding a core of three ribonucleoproteins (RNPs) (9). These RNPs are complexes of nucleoprotein (N), RNA-dependent RNA polymerase (L), and a viral genomic RNA (vRNA).…”

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confidence: 99%

Virulence Factor NSs of Rift Valley Fever Virus Recruits the F-Box Protein FBXO3 To Degrade Subunit p62 of General Transcription Factor TFIIH

Kainulainen

Habjan

Hubel

et al. 2014

J Virol

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The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. IMPORTANCERift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity.

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Molecular Biology of Rift Valley Fever Virus

Cited by 66 publications

References 96 publications

RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila

RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila

Argonaute 2 Suppresses Japanese Encephalitis Virus Infection in <i>Aedes aegypti</i>

Virulence Factor NSs of Rift Valley Fever Virus Recruits the F-Box Protein FBXO3 To Degrade Subunit p62 of General Transcription Factor TFIIH

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