Shared transcriptomic responses of Aedes aegypti to arboviral infections : example of dengue and Rift Valley fever viruses

Abstract BackgroundArthropod borne virus infections cause several emerging and resurgent infectious diseases. Among the diseases caused by arboviruses, dengue and Rift Valley fever are responsible for a high rate of severe human diseases worldwide. Understanding the effects of viral infection on gene expression in the mosquito is crucial to the development of early diagnostic tools and may enable researchers and policy makers to better anticipate outbreaks in the next future. Methods Here we investigate the alterations in gene expression across the entire Aedes aegypti genome during infection with DENV and RVF over time.ResultsWe describe several up-regulated genes that share a similar expression profile during infection with both viruses at early and late phases of infection. Family B and D clip-domain serine proteases (CLIP) are clearly overrepresented as well as C-type lectins and transferrin. ConclusionsOur results provide an extensive amount of data highlighting viral gene targets in the mosquito during infection. This data may also be used to develop broad-spectrum anti-viral diagnostic tools based on mosquitoes rather than the mammalian hosts and would help to predict and manage the emergence of outbreaks.

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The Nonstructural Protein NSs Induces a Variable Antibody Response in Domestic Ruminants Naturally Infected with Rift Valley Fever Virus

Clinical and Vaccine Immunology ◽

10.1128/cvi.05420-11 ◽

2011 ◽

Vol 19 (1) ◽

pp. 5-10 ◽

Cited By ~ 12

Author(s):

José-Carlos Fernandez ◽

Agnès Billecocq ◽

Jean Paul Durand ◽

Catherine Cêtre-Sossah ◽

Eric Cardinale ◽

...

Keyword(s):

Antibody Response ◽

Rift Valley ◽

Rift Valley Fever ◽

Nonstructural Protein ◽

Rift Valley Fever Virus ◽

High Rate ◽

Antibody Detection ◽

Enzyme Linked Immunosorbent Assay ◽

Valley Fever ◽

Wide Range

ABSTRACTRift Valley fever (RVF) is an emerging zoonosis in Africa which has spread to Egypt, the Arabian Peninsula, Madagascar, and Comoros. RVF virus (RVFV) (Bunyaviridaefamily,Phlebovirusgenus) causes a wide range of symptoms in humans, from benign fever to fatal hemorrhagic fever. Ruminants are severely affected by the disease, which leads to a high rate of mortality in young animals and to abortions and teratogenesis in pregnant females. Diagnostic tests include virus isolation and genome or antibody detection. During RVFV infection, the nucleoprotein encapsidating the tripartite RNA genome is expressed in large amounts and raises a robust antibody response, while the envelope glycoproteins elicit neutralizing antibodies which play a major role in protection. Much less is known about the antigenicity/immunogenicity of the nonstructural protein NSs, which is a major virulence factor. Here we have developed a competitive enzyme-linked immunosorbent assay (ELISA) enabling detection of low levels of NSs-specific antibodies in naturally infected or vaccinated ruminants. Detection of the NSs antibodies was validated by Western blotting. Altogether, our data showed that the NSs antibodies were detected in only 55% of animals naturally infected by RVFV, indicating that NSs does not induce a consistently high immune response. These results are discussed in light of differentiation between infected and vaccinated animals (DIVA) tests distinguishing naturally infected animals and those vaccinated with NSs-defective vaccines.

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NSs Protein of Rift Valley Fever Virus Blocks Interferon Production by Inhibiting Host Gene Transcription

Journal of Virology ◽

10.1128/jvi.78.18.9798-9806.2004 ◽

2004 ◽

Vol 78 (18) ◽

pp. 9798-9806 ◽

Cited By ~ 234

Author(s):

Agnès Billecocq ◽

Martin Spiegel ◽

Pierre Vialat ◽

Alain Kohl ◽

Friedemann Weber ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Rift Valley ◽

Rift Valley Fever ◽

Rift Valley Fever Virus ◽

Fever Virus ◽

Poly I:C ◽

Transcriptional Level ◽

Mobility Shift ◽

Valley Fever

ABSTRACT Rift Valley fever virus (RVFV) is an important cause of epizootics and epidemics in Africa and a potential agent of bioterrorism. A better understanding of the factors that govern RVFV virulence and pathogenicity is required, given the urgent need for antiviral therapies and safe vaccines. We have previously shown that RVFV strains with mutations in the NSs gene are excellent inducers of α/β interferon (IFN-α/β) and are highly attenuated in mice. Here, we demonstrate that NSs is sufficient to block IFN-β gene expression at the transcriptional level. In cells transiently expressing NSs, IFN-β transcripts were not inducible by viral infection or by transfection of poly(I:C). NSs with anti-IFN activity accumulated in the nucleus. In contrast, mutant forms of NSs that had lost their IFN-inhibiting activity remained in the cytoplasm, indicating that nuclear localization plays a role. IFN synthesis is regulated by specific transcription factors, including interferon regulatory factor (IRF-3), NF-κB, and AP-1. In the presence of NSs, IRF-3 was still activated and moved to the nucleus. Likewise, NF-κB and AP-1 were activated normally, as shown in electrophoretic mobility shift assays. Moreover, NSs was found to inhibit transcriptional activity of a constitutive promoter, in agreement with recent findings showing that NSs targets the basal cellular transcription factor TFIIH. The present results suggest that NSs, unlike other viral IFN antagonists, does not inhibit IFN-specific transcription factors but blocks IFN gene expression at a subsequent step.

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Interplay between the Virus and Host in Rift Valley Fever Pathogenesis

Journal of Innate Immunity ◽

10.1159/000373924 ◽

2015 ◽

Vol 7 (5) ◽

pp. 450-458 ◽

Cited By ~ 13

Author(s):

Kaori Terasaki ◽

Shinji Makino

Keyword(s):

Rift Valley ◽

Rift Valley Fever ◽

Current Knowledge ◽

Rift Valley Fever Virus ◽

Severe Disease ◽

Model Systems ◽

High Rate ◽

Valley Fever ◽

Middle East Countries ◽

Biosafety Level

Rift Valley fever virus (RVFV) belongs to the genus Phlebovirus, family Bunyaviridae, and carries single-stranded tripartite RNA segments. The virus is transmitted by mosquitoes and has caused large outbreaks among ruminants and humans in sub-Saharan African and Middle East countries. The disease is characterized by a sudden onset of fever, headache, muscle pain, joint pain, photophobia, and weakness. In most cases, patients recover from the disease after a period of weeks, but some also develop retinal or macular changes, which result in vision impairment that lasts for an undefined period of time, and severe disease, characterized by hemorrhagic fever or encephalitis. The virus also causes febrile illness resulting in a high rate of spontaneous abortions in ruminants. The handling of wild-type RVFV requires high-containment facilities, including biosafety level 4 or enhanced biosafety level 3 laboratories. Nonetheless, studies clarifying the mechanisms of the RVFV-induced diseases and preventing them are areas of active research throughout the world. By primarily referring to recent studies using several animal model systems, protein expression systems, and specific mutant viruses, this review describes the current knowledge about the mechanisms of pathogenesis of RVF and biological functions of various viral proteins that affect RVFV pathogenicity.

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Rift Valley Fever Virus L Protein Forms a Biologically Active Oligomer

Journal of Virology ◽

10.1128/jvi.01310-09 ◽

2009 ◽

Vol 83 (24) ◽

pp. 12779-12789 ◽

Cited By ~ 30

Author(s):

Aya Zamoto-Niikura ◽

Kaori Terasaki ◽

Tetsuro Ikegami ◽

C. J. Peters ◽

Shinji Makino

Keyword(s):

Rift Valley ◽

Rift Valley Fever ◽

Rift Valley Fever Virus ◽

Fever Virus ◽

Dominant Negative ◽

Biologically Active ◽

Bimolecular Fluorescence Complementation ◽

Viral Gene ◽

Valley Fever ◽

L Protein

ABSTRACT Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) causes mosquito-borne epidemic diseases in humans and livestock. The virus carries three RNA segments, L, M, and S, of negative or ambisense polarity. L protein, an RNA-dependent RNA polymerase, encoded in the L segment, and N protein, encoded in the S segment, exert viral RNA replication and transcription. Coexpression of N, hemagglutinin (HA)-tagged L, and viral minigenome resulted in minigenome replication and transcription, a finding that demonstrated HA-tagged L was biologically active. Likewise L tagged with green fluorescent protein (GFP) was biologically competent. Coimmunoprecipitation analysis using extracts from cells coexpressing HA-tagged L and GFP-tagged L showed the formation of an L oligomer. Bimolecular fluorescence complementation analysis and coimmunoprecipitation studies demonstrated the formation of an intermolecular L-L interaction through its N-terminal and C-terminal regions and also suggested an intramolecular association between the N-terminal and C-terminal regions of L protein. A biologically inactive L mutant, in which the conserved signature SDD motif was replaced by the amino acid residues GNN, exhibited a dominant negative phenotype when coexpressed with wild-type L in the minigenome assay system. Expression of this mutant L also inhibited viral gene expression in virus-infected cells. These data provided compelling evidence for the importance of oligomerization of RVFV L protein for its polymerase activity.

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