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Dr. Esther Schnettler
Bernhard Nocht Institut fur Tropenmedizin Hamburg, 20359 Hamburg, Germany

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0 virus-host interactions
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0 arboviruses
0 Bunyavirales
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Journal article
Published: 03 June 2021 in Viruses
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Mosquitoes are known as important vectors of many arthropod-borne (arbo)viruses causing disease in humans. These include dengue (DENV) and Zika (ZIKV) viruses. The exogenous small interfering (si)RNA (exo-siRNA) pathway is believed to be the main antiviral defense in arthropods, including mosquitoes. During infection, double-stranded RNAs that form during viral replication and infection are cleaved by the enzyme Dicer 2 (Dcr2) into virus-specific 21 nt vsiRNAs, which are subsequently loaded into Argonaute 2 (Ago2). Ago2 then targets and subsequently cleaves complementary RNA sequences, resulting in degradation of the target viral RNA. Although various studies using silencing approaches have supported the antiviral activity of the exo-siRNA pathway in mosquitoes, and despite strong similarities between the siRNA pathway in the Drosophila melanogaster model and mosquitoes, important questions remain unanswered. The antiviral activity of Ago2 against different arboviruses has been previously demonstrated. However, silencing of Ago2 had no effect on ZIKV replication, whereas Dcr2 knockout enhanced its replication. These findings raise the question as to the role of Ago2 and Dcr2 in the control of arboviruses from different viral families in mosquitoes. Using a newly established Ago2 knockout cell line, alongside the previously reported Dcr2 knockout cell line, we investigated the impact these proteins have on the modulation of different arboviral infections. Infection of Ago2 knockout cell line with alpha- and bunyaviruses resulted in an increase of viral replication, but not in the case of ZIKV. Analysis of small RNA sequencing data in the Ago2 knockout cells revealed a lack of methylated siRNAs from different sources, such as acute and persistently infecting viruses-, TE- and transcriptome-derived RNAs. The results confirmed the importance of the exo-siRNA pathway in the defense against arboviruses, but highlights variability in its response to different viruses and the impact the siRNA pathway proteins have in controlling viral replication. Moreover, this established Ago2 knockout cell line can be used for functional Ago2 studies, as well as research on the interplay between the RNAi pathways.

ACS Style

Christina Scherer; Jack Knowles; Vattipally Sreenu; Anthony Fredericks; Janina Fuss; Kevin Maringer; Ana Fernandez-Sesma; Andres Merits; Margus Varjak; Alain Kohl; Esther Schnettler. An Aedes aegypti-Derived Ago2 Knockout Cell Line to Investigate Arbovirus Infections. Viruses 2021, 13, 1066 .

AMA Style

Christina Scherer, Jack Knowles, Vattipally Sreenu, Anthony Fredericks, Janina Fuss, Kevin Maringer, Ana Fernandez-Sesma, Andres Merits, Margus Varjak, Alain Kohl, Esther Schnettler. An Aedes aegypti-Derived Ago2 Knockout Cell Line to Investigate Arbovirus Infections. Viruses. 2021; 13 (6):1066.

Chicago/Turabian Style

Christina Scherer; Jack Knowles; Vattipally Sreenu; Anthony Fredericks; Janina Fuss; Kevin Maringer; Ana Fernandez-Sesma; Andres Merits; Margus Varjak; Alain Kohl; Esther Schnettler. 2021. "An Aedes aegypti-Derived Ago2 Knockout Cell Line to Investigate Arbovirus Infections." Viruses 13, no. 6: 1066.

Journal article
Published: 11 July 2020 in Viruses
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Mosquitoes, such as Aedes aegypti, can transmit arboviruses to humans. The exogenous short interfering RNA (exo-siRNA) pathway plays a major antiviral role in controlling virus infection in mosquito cells. The Dicer 2 (Dcr2) nuclease is a key effector protein in this pathway, which cleaves viral double-stranded RNA into virus-derived siRNAs that are further loaded onto an effector called Argonaute 2 (Ago2), which as part of the multiprotein RNA-induced silencing complex (RISC) targets and cleaves viral RNA. In order to better understand the effector protein Dcr2, proteomics experiments were conducted to identify interacting cellular partners. We identified several known interacting partners including Ago2, as well as two novel and previously uncharacterized Ae. aegypti proteins. The role of these two proteins was further investigated, and their interactions with Dcr2 verified by co-immunoprecipitation. Interestingly, despite their ability to interact with Ago2 and Piwi4, neither of these proteins was found to affect exo-siRNA silencing in a reporter assay. However, one of these proteins, Q0IFK9, subsequently called aBravo (aedine broadly active antiviral protein), was found to mediate antiviral activity against positive strand RNA arboviruses. Intriguingly the presence of Dcr2 was not necessary for this effect, suggesting that this interacting antiviral effector may act as part of protein complexes with potentially separate antiviral activities.

ACS Style

Margus Varjak; Rommel Gestuveo; Richard Burchmore; Esther Schnettler; Alain Kohl. aBravo Is a Novel Aedes aegypti Antiviral Protein that Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2. Viruses 2020, 12, 748 .

AMA Style

Margus Varjak, Rommel Gestuveo, Richard Burchmore, Esther Schnettler, Alain Kohl. aBravo Is a Novel Aedes aegypti Antiviral Protein that Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2. Viruses. 2020; 12 (7):748.

Chicago/Turabian Style

Margus Varjak; Rommel Gestuveo; Richard Burchmore; Esther Schnettler; Alain Kohl. 2020. "aBravo Is a Novel Aedes aegypti Antiviral Protein that Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2." Viruses 12, no. 7: 748.

Journal article
Published: 14 April 2020 in Viruses
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The inland floodwater mosquito Aedes vexans (Meigen, 1830) is a competent vector of numerous arthropod-borne viruses such as Rift Valley fever virus (Phenuiviridae) and Zika virus (Flaviviridae). Aedes vexans spp. have widespread Afrotropical distribution and are common European cosmopolitan mosquitoes. We examined the virome of Ae. vexans arabiensis samples from Barkédji village, Senegal, with small RNA sequencing, bioinformatic analysis, and RT-PCR screening. We identified a novel 9494 nt iflavirus (Picornaviridae) designated here as Aedes vexans iflavirus (AvIFV). Annotation of the AvIFV genome reveals a 2782 amino acid polyprotein with iflavirus protein domain architecture and typical iflavirus 5’ internal ribosomal entry site and 3’ poly-A tail. Aedes vexans iflavirus is most closely related to a partial virus sequence from Venturia canescens (a parasitoid wasp) with 56.77% pairwise amino acid identity. Analysis of AvIFV-derived small RNAs suggests that AvIFV is targeted by the exogenous RNA interference pathway but not the PIWI-interacting RNA response, as ~60% of AvIFV reads corresponded to 21 nt Dicer-2 virus-derived small RNAs and the 24–29 nt AvIFV read population did not exhibit a “ping-pong” signature. The RT-PCR screens of archival and current (circa 2011–2020) Ae. vexans arabiensis laboratory samples and wild-caught mosquitoes from Barkédji suggest that AvIFV is ubiquitous in these mosquitoes. Further, we screened wild-caught European Ae. vexans samples from Germany, the United Kingdom, Italy, and Sweden, all of which tested negative for AvIFV RNA. This report provides insight into the diversity of commensal Aedes viruses and the host RNAi response towards iflaviruses.

ACS Style

Rhys Parry; Fanny Naccache; El Hadji Ndiaye; Gamou Fall; Ilaria Castelli; Renke Lühken; Jolyon Medlock; Benjamin Cull; Jenny C. Hesson; Fabrizio Montarsi; Anna-Bella Failloux; Alain Kohl; Esther Schnettler; Mawlouth Diallo; Sassan Asgari; Isabelle Dietrich; Stefanie C. Becker. Identification and RNAi Profile of a Novel Iflavirus Infecting Senegalese Aedes vexans arabiensis Mosquitoes. Viruses 2020, 12, 440 .

AMA Style

Rhys Parry, Fanny Naccache, El Hadji Ndiaye, Gamou Fall, Ilaria Castelli, Renke Lühken, Jolyon Medlock, Benjamin Cull, Jenny C. Hesson, Fabrizio Montarsi, Anna-Bella Failloux, Alain Kohl, Esther Schnettler, Mawlouth Diallo, Sassan Asgari, Isabelle Dietrich, Stefanie C. Becker. Identification and RNAi Profile of a Novel Iflavirus Infecting Senegalese Aedes vexans arabiensis Mosquitoes. Viruses. 2020; 12 (4):440.

Chicago/Turabian Style

Rhys Parry; Fanny Naccache; El Hadji Ndiaye; Gamou Fall; Ilaria Castelli; Renke Lühken; Jolyon Medlock; Benjamin Cull; Jenny C. Hesson; Fabrizio Montarsi; Anna-Bella Failloux; Alain Kohl; Esther Schnettler; Mawlouth Diallo; Sassan Asgari; Isabelle Dietrich; Stefanie C. Becker. 2020. "Identification and RNAi Profile of a Novel Iflavirus Infecting Senegalese Aedes vexans arabiensis Mosquitoes." Viruses 12, no. 4: 440.

Research article
Published: 27 September 2019 in PLOS Neglected Tropical Diseases
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Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus (Flaviviridae), is a causative agent of a severe neuroinfection. Recently, several flaviviruses have been shown to interact with host protein synthesis. In order to determine whether TBEV interacts with this host process in its natural target cells, we analysed de novo protein synthesis in a human cell line derived from cerebellar medulloblastoma (DAOY HTB-186). We observed a significant decrease in the rate of host protein synthesis, including the housekeeping genes HPRT1 and GAPDH and the known interferon-stimulated gene viperin. In addition, TBEV infection resulted in a specific decrease of RNA polymerase I (POLR1) transcripts, 18S and 28S rRNAs and their precursor, 45-47S pre-rRNA, but had no effect on the POLR3 transcribed 5S rRNA levels. To our knowledge, this is the first report of flavivirus-induced decrease of specifically POLR1 rRNA transcripts accompanied by host translational shut-off.

ACS Style

Martin Selinger; Hana Tykalová; Jan Sterba; Pavlína Věchtová; Zuzana Vavrušková; Jaroslava Lieskovská; Alain Kohl; Esther Schnettler; Libor Grubhoffer. Tick-borne encephalitis virus inhibits rRNA synthesis and host protein production in human cells of neural origin. PLOS Neglected Tropical Diseases 2019, 13, e0007745 .

AMA Style

Martin Selinger, Hana Tykalová, Jan Sterba, Pavlína Věchtová, Zuzana Vavrušková, Jaroslava Lieskovská, Alain Kohl, Esther Schnettler, Libor Grubhoffer. Tick-borne encephalitis virus inhibits rRNA synthesis and host protein production in human cells of neural origin. PLOS Neglected Tropical Diseases. 2019; 13 (9):e0007745.

Chicago/Turabian Style

Martin Selinger; Hana Tykalová; Jan Sterba; Pavlína Věchtová; Zuzana Vavrušková; Jaroslava Lieskovská; Alain Kohl; Esther Schnettler; Libor Grubhoffer. 2019. "Tick-borne encephalitis virus inhibits rRNA synthesis and host protein production in human cells of neural origin." PLOS Neglected Tropical Diseases 13, no. 9: e0007745.

Review
Published: 17 September 2019 in Viruses
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Mosquito-specific viruses (MSVs) are a subset of insect-specific viruses that are found to infect mosquitoes or mosquito derived cells. There has been an increase in discoveries of novel MSVs in recent years. This has expanded our understanding of viral diversity and evolution but has also sparked questions concerning the transmission of these viruses and interactions with their hosts and its microbiome. In fact, there is already evidence that MSVs interact with the immune system of their host. This is especially interesting, since mosquitoes can be infected with both MSVs and arthropod-borne (arbo) viruses of public health concern. In this review, we give an update on the different MSVs discovered so far and describe current data on their transmission and interaction with the mosquito immune system as well as the effect MSVs could have on an arboviruses-co-infection. Lastly, we discuss potential uses of these viruses, including vector and transmission control.

ACS Style

Eric Agboli; Mayke Leggewie; Mine Altinli; Esther Schnettler. Mosquito-Specific Viruses—Transmission and Interaction. Viruses 2019, 11, 873 .

AMA Style

Eric Agboli, Mayke Leggewie, Mine Altinli, Esther Schnettler. Mosquito-Specific Viruses—Transmission and Interaction. Viruses. 2019; 11 (9):873.

Chicago/Turabian Style

Eric Agboli; Mayke Leggewie; Mine Altinli; Esther Schnettler. 2019. "Mosquito-Specific Viruses—Transmission and Interaction." Viruses 11, no. 9: 873.

Journal article
Published: 17 September 2019 in Viruses
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Biting midges (Culicoides species) are vectors of arboviruses and were responsible for the emergence and spread of Schmallenberg virus (SBV) in Europe in 2011 and are likely to be involved in the emergence of other arboviruses in Europe. Improved surveillance and better understanding of risks require a better understanding of the circulating viral diversity in these biting insects. In this study, we expand the sequence space of RNA viruses by identifying a number of novel RNA viruses from Culicoides impunctatus (biting midge) using a meta-transcriptomic approach. A novel metaviromic pipeline called MetaViC was developed specifically to identify novel virus sequence signatures from high throughput sequencing (HTS) datasets in the absence of a known host genome. MetaViC is a protein centric pipeline that looks for specific protein signatures in the reads and contigs generated as part of the pipeline. Several novel viruses, including an alphanodavirus with both segments, a novel relative of the Hubei sobemo-like virus 49, two rhabdo-like viruses and a chuvirus, were identified in the Scottish midge samples. The newly identified viruses were found to be phylogenetically distinct to those previous known. These findings expand our current knowledge of viral diversity in arthropods and especially in these understudied disease vectors.

ACS Style

Sejal Modha; Joseph Hughes; Giovanni Bianco; Heather M. Ferguson; Barbara Helm; Lily Tong; Gavin S. Wilkie; Alain Kohl; Esther Schnettler. Metaviromics Reveals Unknown Viral Diversity in the Biting Midge Culicoides impunctatus. Viruses 2019, 11, 865 .

AMA Style

Sejal Modha, Joseph Hughes, Giovanni Bianco, Heather M. Ferguson, Barbara Helm, Lily Tong, Gavin S. Wilkie, Alain Kohl, Esther Schnettler. Metaviromics Reveals Unknown Viral Diversity in the Biting Midge Culicoides impunctatus. Viruses. 2019; 11 (9):865.

Chicago/Turabian Style

Sejal Modha; Joseph Hughes; Giovanni Bianco; Heather M. Ferguson; Barbara Helm; Lily Tong; Gavin S. Wilkie; Alain Kohl; Esther Schnettler. 2019. "Metaviromics Reveals Unknown Viral Diversity in the Biting Midge Culicoides impunctatus." Viruses 11, no. 9: 865.

Journal article
Published: 06 December 2018 in Viruses
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Arthropod vectors control the replication of arboviruses through their innate antiviral immune responses. In particular, the RNA interference (RNAi) pathways are of notable significance for the control of viral infections. Although much has been done to understand the role of RNAi in vector populations, little is known about its importance in non-vector mosquito species. In this study, we investigated the presence of an RNAi response in Toxorhynchites amboinensis, which is a non-blood feeding species proposed as a biological control agent against pest mosquitoes. Using a derived cell line (TRA-171), we demonstrate that these mosquitoes possess a functional RNAi response that is active against a mosquito-borne alphavirus, Semliki Forest virus. As observed in vector mosquito species, small RNAs are produced that target viral sequences. The size and characteristics of these small RNAs indicate that both the siRNA and piRNA pathways are induced in response to infection. Taken together, this data suggests that Tx. amboinensis are able to control viral infections in a similar way to natural arbovirus vector mosquito species. Understanding their ability to manage arboviral infections will be advantageous when assessing these and similar species as biological control agents.

ACS Style

Claire L. Donald; Margus Varjak; Eric Roberto Guimarães Rocha Aguiar; João T. Marques; Vattipally B. Sreenu; Esther Schnettler; Alain Kohl. Antiviral RNA Interference Activity in Cells of the Predatory Mosquito, Toxorhynchites amboinensis. Viruses 2018, 10, 694 .

AMA Style

Claire L. Donald, Margus Varjak, Eric Roberto Guimarães Rocha Aguiar, João T. Marques, Vattipally B. Sreenu, Esther Schnettler, Alain Kohl. Antiviral RNA Interference Activity in Cells of the Predatory Mosquito, Toxorhynchites amboinensis. Viruses. 2018; 10 (12):694.

Chicago/Turabian Style

Claire L. Donald; Margus Varjak; Eric Roberto Guimarães Rocha Aguiar; João T. Marques; Vattipally B. Sreenu; Esther Schnettler; Alain Kohl. 2018. "Antiviral RNA Interference Activity in Cells of the Predatory Mosquito, Toxorhynchites amboinensis." Viruses 10, no. 12: 694.

Review article
Published: 01 October 2018 in Current Opinion in Virology
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Antiviral RNA interference (RNAi) in insects is known for some time. Previously, data from the model organism Drosophila was lightly transferred to other insects. However, since more research is performed on other insects, both similarities and important differences among the RNAi pathways of insects are revealed. The piRNA pathway, for example, is suggested to have antiviral functions in mosquitoes, which is unknown for other insects. Moreover, production of viral cDNA from RNA viruses during infection and their possible incorporation into the genome hint towards potential inheritable immunity in mosquitoes. Increased knowledge of antiviral RNAi pathways has initiated efforts to engineer insects resistant to viral infections. New advances in genome editing will further stimulate this process.

ACS Style

Mayke Leggewie; Esther Schnettler. RNAi-mediated antiviral immunity in insects and their possible application. Current Opinion in Virology 2018, 32, 108 -114.

AMA Style

Mayke Leggewie, Esther Schnettler. RNAi-mediated antiviral immunity in insects and their possible application. Current Opinion in Virology. 2018; 32 ():108-114.

Chicago/Turabian Style

Mayke Leggewie; Esther Schnettler. 2018. "RNAi-mediated antiviral immunity in insects and their possible application." Current Opinion in Virology 32, no. : 108-114.

Journal article
Published: 18 February 2018 in Viruses
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Mosquitoes transmit several human- and animal-pathogenic alphaviruses (Togaviridae family). In alphavirus-infected mosquito cells two different types of virus-specific small RNAs are produced as part of the RNA interference response: short-interfering (si)RNAs and PIWI-interacting (pi)RNAs. The siRNA pathway is generally thought to be the main antiviral pathway. Although an antiviral activity has been suggested for the piRNA pathway its role in host defences is not clear. Knock down of key proteins of the piRNA pathway (Ago3 and Piwi5) in Aedes aegypti-derived cells reduced the production of alphavirus chikungunya virus (CHIKV)-specific piRNAs but had no effect on virus replication. In contrast, knock down of the siRNA pathway key protein Ago2 resulted in an increase in virus replication. Similar results were obtained when expression of Piwi4 was silenced. Knock down of the helicase Spindle-E (SpnE), an essential co-factor of the piRNA pathway in Drosophila melanogaster, resulted in increased virus replication indicating that SpnE acts as an antiviral against alphaviruses such as CHIKV and the related Semliki Forest virus (SFV). Surprisingly, this effect was found to be independent of the siRNA and piRNA pathways in Ae. aegypti cells and specific for alphaviruses. This suggests a small RNA-independent antiviral function for this protein in mosquitoes.

ACS Style

Margus Varjak; Isabelle Dietrich; Vattipally B. Sreenu; Bethan Eluned Till; Andres Merits; Alain Kohl; Esther Schnettler. Spindle-E Acts Antivirally Against Alphaviruses in Mosquito Cells. Viruses 2018, 10, 88 .

AMA Style

Margus Varjak, Isabelle Dietrich, Vattipally B. Sreenu, Bethan Eluned Till, Andres Merits, Alain Kohl, Esther Schnettler. Spindle-E Acts Antivirally Against Alphaviruses in Mosquito Cells. Viruses. 2018; 10 (2):88.

Chicago/Turabian Style

Margus Varjak; Isabelle Dietrich; Vattipally B. Sreenu; Bethan Eluned Till; Andres Merits; Alain Kohl; Esther Schnettler. 2018. "Spindle-E Acts Antivirally Against Alphaviruses in Mosquito Cells." Viruses 10, no. 2: 88.

Tropenmedizin
Published: 12 December 2017 in Flugmedizin · Tropenmedizin · Reisemedizin - FTR
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Die molekulare Entomologie ist ein neuer Forschungszweig, der die klassische Insektenkunde mehr an molekulare Forschung und Techniken heranführt. Neben neuen Möglichkeiten für die Taxonomie, haben sich auch neue Türen für die Grundlagenforschung geöffnet. Beispielsweise konnte das Grundlagenwissen über das Immunsystem der Insekten und ihre Interaktionen mit Mikroben und Pathogenen extrem erweitert werden. Dies ist besonders wichtig im Kampf gegen die Ausbreitung von insektenübertragenden Pathogenen. In diesem Artikel stellen wir, am Beispiel der Stechmücke, neueste Erkenntnisse der molekularen Entomologie und ihre wichtige Rolle bei der Eindämmung von Infektionskrankheiten vor.

ACS Style

Mayke Leggewie; Esther Schnettler. Molekulare Entomologie: neue Techniken zur Erforschung von vektorübertragenden Infektionskrankheiten. Flugmedizin · Tropenmedizin · Reisemedizin - FTR 2017, 24, 274 -277.

AMA Style

Mayke Leggewie, Esther Schnettler. Molekulare Entomologie: neue Techniken zur Erforschung von vektorübertragenden Infektionskrankheiten. Flugmedizin · Tropenmedizin · Reisemedizin - FTR. 2017; 24 (6):274-277.

Chicago/Turabian Style

Mayke Leggewie; Esther Schnettler. 2017. "Molekulare Entomologie: neue Techniken zur Erforschung von vektorübertragenden Infektionskrankheiten." Flugmedizin · Tropenmedizin · Reisemedizin - FTR 24, no. 6: 274-277.

Journal article
Published: 28 June 2017 in mSphere
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Mosquitoes transmit several pathogenic viruses, for example, the chikungunya and Zika viruses. In mosquito cells, virus replication intermediates in the form of double-stranded RNA are cleaved by Dcr2 into 21-nucleotide-long siRNAs, which in turn are used by Ago2 to target the virus genome. A different class of virus-derived small RNAs, PIWI-interacting RNAs (piRNAs), have also been found in infected insect cells. These piRNAs are longer and are produced in a Dcr2-independent manner. The only known antiviral protein in the PIWI family is Piwi4, which is not involved in piRNA production. It is associated with key proteins of the siRNA and piRNA pathways, although its antiviral function is independent of their actions.

ACS Style

Margus Varjak; Kevin Maringer; Mick Watson; Vattipally B. Sreenu; Anthony C. Fredericks; Emilie Pondeville; Claire Donald; Jelle Sterk; Joy Kean; Marie Vazeille; Anna-Bella Failloux; Alain Kohl; Esther Schnettler. Aedes aegypti Piwi4 Is a Noncanonical PIWI Protein Involved in Antiviral Responses. mSphere 2017, 2, e00144-17 .

AMA Style

Margus Varjak, Kevin Maringer, Mick Watson, Vattipally B. Sreenu, Anthony C. Fredericks, Emilie Pondeville, Claire Donald, Jelle Sterk, Joy Kean, Marie Vazeille, Anna-Bella Failloux, Alain Kohl, Esther Schnettler. Aedes aegypti Piwi4 Is a Noncanonical PIWI Protein Involved in Antiviral Responses. mSphere. 2017; 2 (3):e00144-17.

Chicago/Turabian Style

Margus Varjak; Kevin Maringer; Mick Watson; Vattipally B. Sreenu; Anthony C. Fredericks; Emilie Pondeville; Claire Donald; Jelle Sterk; Joy Kean; Marie Vazeille; Anna-Bella Failloux; Alain Kohl; Esther Schnettler. 2017. "Aedes aegypti Piwi4 Is a Noncanonical PIWI Protein Involved in Antiviral Responses." mSphere 2, no. 3: e00144-17.

Journal article
Published: 06 January 2017 in PLOS Neglected Tropical Diseases
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Vector 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. The 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. These findings have important implications for our understanding of antiviral RNAi pathways and orthobunyavirus-vector interactions and tropism. A number of orthobunyaviruses such as Oropouche virus, La Crosse virus and Schmallenberg virus are important global human or animal pathogens transmitted by arthropod vectors. Further understanding of the antiviral control mechanisms in arthropod vectors is key to developing novel prevention strategies based on preventing transmission. Antiviral small RNA pathways such as the exogenous siRNA and piRNA pathways have been shown to mediate antiviral activity against positive-strand RNA arboviruses, but information about their activities against negative-strand RNA arboviruses is critically lacking. Here we show that in Aedes aegypti-derived mosquito cells, the antiviral responses to mosquito-borne orthobunyaviruses is largely mediated by both siRNA and piRNA pathways, whereas the piRNA pathway plays only a minor role in controlling midge-borne orthobunyaviruses. This suggests that vector specificity is in part controlled by antiviral responses that depend on the host species. These findings contribute significantly to our understanding of arbovirus-vector interactions.

ACS Style

Isabelle Dietrich; Xiaohong Shi; Melanie McFarlane; Mick Watson; Anne-Lie Blomström; Jessica K. Skelton; Alain Kohl; Richard M. Elliott; Esther Schnettler. The Antiviral RNAi Response in Vector and Non-vector Cells against Orthobunyaviruses. PLOS Neglected Tropical Diseases 2017, 11, e0005272 .

AMA Style

Isabelle Dietrich, Xiaohong Shi, Melanie McFarlane, Mick Watson, Anne-Lie Blomström, Jessica K. Skelton, Alain Kohl, Richard M. Elliott, Esther Schnettler. The Antiviral RNAi Response in Vector and Non-vector Cells against Orthobunyaviruses. PLOS Neglected Tropical Diseases. 2017; 11 (1):e0005272.

Chicago/Turabian Style

Isabelle Dietrich; Xiaohong Shi; Melanie McFarlane; Mick Watson; Anne-Lie Blomström; Jessica K. Skelton; Alain Kohl; Richard M. Elliott; Esther Schnettler. 2017. "The Antiviral RNAi Response in Vector and Non-vector Cells against Orthobunyaviruses." PLOS Neglected Tropical Diseases 11, no. 1: e0005272.

Journal article
Published: 10 November 2016 in Journal of General Virology
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Mosquito-borne viruses are known to cause disease in humans and livestock and are often difficult to control due to the lack of specific antivirals and vaccines. The Wolbachia endosymbiont has been widely studied for its ability to restrict positive-strand RNA virus infection in mosquitoes, although little is known about the precise antiviral mechanism. In recent years, a variety of insect-specific viruses have been discovered in mosquitoes and an interaction with mosquito-borne viruses has been reported for some of them; however, nothing is known about the effect of Wolbachia on insect-specific virus infection in mosquitoes. Here, we show that transinfection of the Drosophila-derived wMelPop Wolbachia strain into Aedes aegypti-derived cells resulted in inhibition and even clearance of the persistent cell-fusing agent flavivirus infection in these cells. This broadens the antiviral activity of Wolbachia from acute infections to persistent infections and from arboviruses to mosquito-specific viruses. In contrast, no effect on the Phasi Charoen-like bunyavirus persistent infection in these cells was observed, suggesting a difference in Wolbachia inhibition between positive- and negative-strand RNA viruses.

ACS Style

Esther Schnettler; Vatipally B. Sreenu; Timothy Mottram; Melanie McFarlane. Wolbachia restricts insect-specific flavivirus infection in Aedes aegypti cells. Journal of General Virology 2016, 97, 3024 -3029.

AMA Style

Esther Schnettler, Vatipally B. Sreenu, Timothy Mottram, Melanie McFarlane. Wolbachia restricts insect-specific flavivirus infection in Aedes aegypti cells. Journal of General Virology. 2016; 97 (11):3024-3029.

Chicago/Turabian Style

Esther Schnettler; Vatipally B. Sreenu; Timothy Mottram; Melanie McFarlane. 2016. "Wolbachia restricts insect-specific flavivirus infection in Aedes aegypti cells." Journal of General Virology 97, no. 11: 3024-3029.