Characterization of Aedes aegypti Innate-Immune Pathways that Limit Chikungunya Virus Replication

McFarlane, Melanie; Arias-Goeta, Camilo; Martin, Estelle; O'Hara, Zoe; Lulla, Aleksei; Mousson, Laurence; Rainey, Stephanie M.; Misbah, Suzana; Schnettler, Esther; Donald, Claire L.; Merits, Andres; Kohl, Alain; Failloux, Anna‐Bella

doi:10.1371/journal.pntd.0002994

Cited by 117 publications

(121 citation statements)

References 48 publications

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“…A continuous insect vector cell line provides a robust system for controlled experiments and has proven to be a reliable model for the study of the innate antiviral immune response to a virus (29,30,(41)(42)(43). Using the WBPH and SBPH cell lines, we showed that SRBSDV is less able to propagate in SBPH cells than in WBPH cells (Fig.…”

Section: Discussionmentioning

confidence: 94%

Small Interfering RNA Pathway Modulates Initial Viral Infection in Midgut Epithelium of Insect after Ingestion of Virus

Lan

Chen

Liu

et al. 2016

J Virol

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IMPORTANCE Many viral pathogens that cause significant global health and agricultural problems are transmitted via insect vectors. The first bottleneck in viral infection, the midgut epithelium, is a principal determinant of the ability of an insect species to transmit a virus. Southern rice black streaked dwarf virus (SRBSDV) is restricted exclusively to the midgut epithelium of an incompetent vector, the small brown planthopper (SBPH).Here, we show that silencing of the core component Dicer-2 of the small interfering RNA (siRNA) pathway increases viral titers in the midgut epithelium past the threshold (1.99 ؋ 10 9 copies of the SRBSDV P10 gene/g of midgut RNA) for viral dissemination into the midgut muscles and then into the salivary glands, allowing the SBPH to become a competent vector of SRBSDV. This result is the first evidence that the siRNA antiviral pathway has a direct role in the control of viral dissemination from the midgut epithelium and that it affects the competence of the virus's vector. Many viral pathogens that cause significant global health and agricultural problems are arthropod borne and transmitted via an insect vector. Many plant viruses are transmitted in a persistent manner by sap-sucking insects, including planthoppers, leafhoppers, thrips, and aphids (1-3). Plant viruses, when ingested by their insect vectors, establish their initial infection in the midgut epithelium, from where they disseminate to the midgut visceral muscles (1-3). The viruses then move from the midgut muscles into the hemolymph and finally into the salivary glands, from where they can be introduced into plant hosts (1-3). Efficient viral infection of the midgut epithelium, where initial infection is established, is thus a determinative factor in the ability of an insect species to transmit a certain plant virus.This ability of an insect species to transmit a virus, which has been described as vector competence, is common in nature (4, 5). For many years, the midgut barrier has been believed to be the principal determinant of vector competence (1-9). For example, infection of the incompetent insect vectors of Rice dwarf virus and SRBSDV, two plant reoviruses, and Tomato spotted wilt virus (TSWV), a tospovirus, is restricted to the midgut epithelium (7-10). The inability of incompetent insect vectors to transmit these viruses may be caused by a failure of the virus to efficiently replicate in or disseminate from the midgut epithelium (1-5). It is possible that viral titers in the midgut epithelium of incompetent vectors are unable to reach the threshold needed for viral dissemination. The innate immune response in the midgut epithelium may effectively control viral accumulation, thus blocking viral transmission by incompetent vectors. However, whether the initial antiviral immune pathway(s) in the insect midgut can modulate the competence of plant virus vectors is not unknown.Several mosquito and Drosophila innate immune responses have been reported to have an antiviral effect. These responses include RNA interfere...

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Section: Discussionmentioning

confidence: 94%

Small Interfering RNA Pathway Modulates Initial Viral Infection in Midgut Epithelium of Insect after Ingestion of Virus

Lan

Chen

Liu

et al. 2016

J Virol

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“…In Drosophila , hop function is required but not sufficient for the activation of Drosophila C virus (DCV)-induced immune genes [53]; similarly, it is possible that the JAK/STAT pathway is involved in the mosquito response against CHIKV and ZIKV, but that additional signals or regulators are also required to efficiently limit infection. CHIKV, in particular, does not appear to activate, and may even suppress, classical insect immune pathways in mosquito cells [8,15,61], suggesting that the mosquito mounts a very different response to this virus compared to DENV. Finally, since CHIKV and ZIKV reached higher infection levels than DENV in our WT mosquitoes, the replication rate of each virus could also have affected the pathway’s efficiency at controlling infection.…”

Section: Discussionmentioning

confidence: 99%

Engineered Aedes aegypti JAK/STAT Pathway-Mediated Immunity to Dengue Virus

et al. 2017

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We have developed genetically modified Ae. aegypti mosquitoes that activate the conserved antiviral JAK/STAT pathway in the fat body tissue, by overexpressing either the receptor Dome or the Janus kinase Hop by the blood feeding-induced vitellogenin (Vg) promoter. Transgene expression inhibits infection with several dengue virus (DENV) serotypes in the midgut as well as systemically and in the salivary glands. The impact of the transgenes Dome and Hop on mosquito longevity was minimal, but it resulted in a compromised fecundity when compared to wild-type mosquitoes. Overexpression of Dome and Hop resulted in profound transcriptome regulation in the fat body tissue as well as the midgut tissue, pinpointing several expression signatures that reflect mechanisms of DENV restriction. Our transcriptome studies and reverse genetic analyses suggested that enrichment of DENV restriction factor and depletion of DENV host factor transcripts likely accounts for the DENV inhibition, and they allowed us to identify novel factors that modulate infection. Interestingly, the fat body-specific activation of the JAK/STAT pathway did not result in any enhanced resistance to Zika virus (ZIKV) or chikungunya virus (CHIKV) infection, thereby indicating a possible specialization of the pathway’s antiviral role.

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“…aegypti Ago2, Piwi4, and Ago1 was performed in Aag2 cells using dsRNAs as previously described [81]. dsRNA targeting eGFP was used as control.…”

Section: Methodsmentioning

confidence: 99%

The Antiviral RNAi Response in Vector and Non-vector Cells against Orthobunyaviruses

et al. 2017

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BackgroundVector arthropods control arbovirus replication and spread through antiviral innate immune responses including RNA interference (RNAi) pathways. Arbovirus infections have been shown to induce the exogenous small interfering RNA (siRNA) and Piwi-interacting RNA (piRNA) pathways, but direct antiviral activity by these host responses in mosquito cells has only been demonstrated against a limited number of positive-strand RNA arboviruses. For bunyaviruses in general, the relative contribution of small RNA pathways in antiviral defences is unknown.Methodology/Principal FindingsThe genus Orthobunyavirus in the Bunyaviridae family harbours a diverse range of mosquito-, midge- and tick-borne arboviruses. We hypothesized that differences in the antiviral RNAi response in vector versus non-vector cells may exist and that could influence viral host range. Using Aedes aegypti-derived mosquito cells, mosquito-borne orthobunyaviruses and midge-borne orthobunyaviruses we showed that bunyavirus infection commonly induced the production of small RNAs and the effects of the small RNA pathways on individual viruses differ in specific vector-arbovirus interactions.Conclusions/SignificanceThese findings have important implications for our understanding of antiviral RNAi pathways and orthobunyavirus-vector interactions and tropism.

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Characterization of Aedes aegypti Innate-Immune Pathways that Limit Chikungunya Virus Replication

Cited by 117 publications

References 48 publications

Small Interfering RNA Pathway Modulates Initial Viral Infection in Midgut Epithelium of Insect after Ingestion of Virus

Small Interfering RNA Pathway Modulates Initial Viral Infection in Midgut Epithelium of Insect after Ingestion of Virus

Engineered Aedes aegypti JAK/STAT Pathway-Mediated Immunity to Dengue Virus

The Antiviral RNAi Response in Vector and Non-vector Cells against Orthobunyaviruses

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