Transgenic Mosquitoes – Fact or Fiction?

Wilke, André Barretto Bruno; Beier, John C.; Benelli, Giovanni

doi:10.1016/j.pt.2018.02.003

Cited by 62 publications

(42 citation statements)

References 81 publications

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“…Despite the theoretical basis for their effectiveness, additional studies are needed to verify the true risks and benefits of programs based on altered mosquitoes. This concern appears to be greater in relation to transgenic mosquitoes, especially on their efficacy, sustainability and impact on the environment and target and non-target species (Wilke et al, 2018).…”

Section: Control and Prophylaxismentioning

confidence: 99%

A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control

et al. 2018

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Chikungunya fever is a mosquito-borne viral illness characterized by a sudden onset of fever associated with joint pains. It was first described in the 1950s during a Chikungunya virus (CHIKV) outbreak in southern Tanzania and has since (re-) emerged and spread to several other geographical areas, reaching large populations and causing massive epidemics. In recent years, CHIKV has gained considerable attention due to its quick spread to the Caribbean and then in the Americas, with many cases reported between 2014 and 2017. CHIKV has further garnered attention due to the clinical diagnostic difficulties when Zika (ZIKV) and dengue (DENV) viruses are simultaneously present. In this review, topical CHIKV-related issues, such as epidemiology and transmission, are examined. The different manifestations of infection (acute, chronic and atypical) are described and a particular focus is placed upon the diagnostic handling in the case of ZIKV and DENV co-circulating. Natural and synthetic compounds under evaluation for treatment of chikungunya disease, including drugs already licensed for other purposes, are also discussed. Finally, previous and current vaccine strategies, as well as the control of the CHIKV transmission through an integrated vector management, are reviewed in some detail.

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Section: Control and Prophylaxismentioning

confidence: 99%

A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control

et al. 2018

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“…JNK pathway can regulate complement system (Garver et al, 2013), apoptosis (McEwen, 2005) and autophagy (Wu et al, 2009). To determine whether JNK pathway induces these functions in SGs, we monitored the impact of Kay silencing on expressions of four TEPs ( TEP20 , TEP24 , TEP15 and TEP2 ), two pro-apoptotic ( Caspase8 and Dronc ) and two autophagy-related ( ATG14 and ATG18A ) genes at 10 dpi with ZIKV.…”

Section: Resultsmentioning

confidence: 99%

JNK pathway restricts DENV, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

Chowdhury

Modahl

Tan

et al. 2020

Preprint

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150 words) 23 Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. 24 However, there is a dearth of knowledge on SG immunity. Here, we characterized SG 25 immune response to dengue, Zika and chikungunya viruses using high-throughput 26 transcriptomics. The three viruses regulate components of Toll, IMD and JNK pathways. 27 However, silencing of Toll and IMD components showed variable effects on SG infection by 28 each virus. In contrast, regulation of JNK pathway produced consistent responses. Virus 29 infection increased with depletion of component Kayak and decreased with depletion of 30 negative regulator Puckered. Virus-induced JNK pathway regulates complement and 31 apoptosis in SGs via TEP20 and Dronc, respectively. Individual and co-silencing of these 32 genes demonstrate their antiviral effects and that both may function together. Co-silencing 33 either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. We 34 identified and characterized the broad antiviral function of JNK pathway in SGs, expanding 35 the immune arsenal that blocks arbovirus transmission. 36 37 38Despite the critical role of SGs in transmission, only three studies have examined DENV-87 responsive differential gene expression in SGs. These studies revealed activation of the Toll 88 5 and IMD pathways (Bonizzoni et al., 2012; Luplertlop et al., 2011; Sim et al., 2012) and 89 identified the anti-DENV functions of Cecropin (Luplertlop et al., 2011), putative Cystatin 90 and ankyrin-repeat proteins (Sim et al., 2012). Here, we characterized the SG immune 91 response to DENV, ZIKV and CHIKV. We performed the first high throughput RNA-92 sequencing (RNA-seq) in infected SGs and observed differentially expressed genes (DEGs) 93 related to immunity, apoptosis, blood-feeding and lipid metabolism. Using gene silencing, we 94 discovered that upregulated components of the Toll and IMD pathways had variable effects 95 against DENV, ZIKV and CHIKV. However, silencing of a JNK pathway upregulated 96 component increased, and silencing of a negative regulator decreased infection by the three 97 viruses in SGs. Further, we show that the JNK pathway is activated by all viruses and triggers 98 a cooperative complement and apoptosis response in SGs. This work identifies and 99 characterizes the JNK antiviral response that reduces DENV, ZIKV and CHIKV in A. aegypti 100 SGs. 101 102 Results 103 Transcriptome regulation by DENV, ZIKV and CHIKV in SGs 104 SGs were collected at 14 days post oral infection (dpi) with DENV and ZIKV, and at seven 105 dpi with CHIKV (Supplementary Figure 1) to account for variability between virus extrinsic 106 incubation periods (EIP) (Mbaika et al., 2016; Salazar et al., 2007). Differentially expressed 107 genes (DEGs) were calculated with DESeq2, edgeR and Cuffdiff 2, and showed little overlap 108 among the algorithms (Supplementary Figure 2). To validate DEGs and select which 109 software to use, we quantified the expression of 10 genes in a biological repeat with RT-1...

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“…Few studies reported the effectiveness of mosquito modification strategies, and even less their eventual effects exploring them only barely and theoretically [13]. Important reviews on this topic were recently published, but corresponding to the perspective of the author regarding the subject or a summary of the authors' selection of publications [14,15]. This work presents a unique structured review on the use of modified insects to control and prevent vector-borne diseases, gathering, exploring, and classifying evidence available up to 2016 regarding efficacy and (non-target) effects of these modifying techniques.…”

Section: Introductionmentioning

confidence: 99%

What happens when we modify mosquitoes for disease prevention? A systematic review

Nazareth

Craveiro

Moutinho

et al. 2020

Emerging Microbes & Infections

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The release of modified mosquitoes to suppress/replace vectors constitutes a promising tool for vector control and disease prevention. Evidence regarding these innovative modification techniques is scarce and disperse. This work conducted a systematic review, gathering and analysing research articles from PubMed and Biblioteca Virtual em Saúde databases whose results report efficacy and non-target effects of using modified insects for disease prevention, until 2016. More than 1500 publications were screened and 349 were analysed. Only 12/3.4% articles reported field-based evidence and 41/11.7% covered modification strategies' post-release efficacy. Variability in the effective results (90/25.7%) questioned its reproducibility in different settings. We also found publications reporting reversal outcomes 38/10.9%, (e.g. post-release increase of vector population). Ecological effects were also reported, such as horizontal transfer events (54/15.5%), and worsening pathogenesis induced by natural wolbachia (10/2.9%). Present work revealed promising outcomes of modifying strategies. However, it also revealed a need for field-based evidence mainly regarding epidemiologic and long-term impact. It pointed out some eventual irreversible and important effects that must not be ignored when considering open-field releases, and that may constitute constraints to generate the missing field evidence. Present work constitutes a baseline of knowledge, offering also a methodological approach that may facilitate future updates.

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Transgenic Mosquitoes – Fact or Fiction?

Cited by 62 publications

References 81 publications

A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control

A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control

JNK pathway restricts DENV, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

What happens when we modify mosquitoes for disease prevention? A systematic review

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