Mosquito microevolution drives Plasmodium falciparum dynamics

Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. However, there is a dearth of knowledge on SG immunity. Here, we characterized SG immune response to dengue, Zika and chikungunya viruses using high-throughput transcriptomics. We also describe a transcriptomic response associated to apoptosis, blood-feeding and lipid metabolism. The three viruses differentially regulate components of Toll, Immune deficiency (IMD) and c-Jun N-terminal Kinase (JNK) pathways. However, silencing of the Toll and IMD pathway components showed variable effects on SG infection by each virus. In contrast, regulation of the JNK pathway produced consistent responses in both SGs and midgut. Infection by the three viruses increased with depletion of the activator Kayak and decreased with depletion of the negative regulator Puckered. Virus-induced JNK pathway regulates the complement factor, Thioester containing protein-20 (TEP20), and the apoptosis activator, Dronc, in SGs. Individual and co-silencing of these genes demonstrate their antiviral effects and that both may function together. Co-silencing either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. Upon infection in SGs, TEP20 induces antimicrobial peptides (AMPs), while Dronc is required for apoptosis independently of TEP20. In conclusion, we revealed the broad antiviral function of JNK pathway in SGs and showed that it is mediated by a TEP20 complement and Dronc-induced apoptosis response. These results expand our understanding of the immune arsenal that blocks arbovirus transmission.

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Section: Discussionmentioning

confidence: 84%

JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

et al. 2020

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“…A recent study established a negative association between the presence of efficient Plasmodium -killing immune response in mosquitoes and epidemics in Africa, confirming the long-suspected impact of mosquito immunity on epidemiology for arthropod-borne diseases (Gildenhard et al, 2019). Upon close inspection of field-derived A. aegypti colony transcriptomes (Sim et al, 2013), we found that DENV-refractory colonies expressed a higher level of Kay, c- Jun and TEP20.…”

Section: Discussionmentioning

confidence: 75%

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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“…Captive mating experiments subsequently demonstrated the discordance was due to the inability to discern A. gambiae from another morphologically identical member of the complex, A. arabiensis (Davidson 1956, Davidson & Jackson, 1962). More recently, Gildenhard et al (2019) noted a striking difference in TEP1 allele frequencies between two populations of A. coluzzii in Burkina Faso, which was attributed to ecologically-varying selection. While this is a very plausible and potentially accurate explanation, the results could also be explained by misidentified AT within the samples, as AT has a very different TEP1 profile from A. coluzzii (Figure 3A, Table 2).…”

Section: Discussionmentioning

confidence: 99%

A population genomic unveiling of a new cryptic mosquito taxon within the malaria-transmittingAnopheles gambiaecomplex

Tennessen

Ingham

Toé

et al. 2020

Preprint

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16 17 The Anopheles gambiae complex consists of multiple morphologically indistinguishable 18 mosquito species including the most important vectors of the malaria parasite Plasmodium 19 falciparum in sub-Saharan Africa. Several lineages have only recently been described as 20 distinct, including the cryptic taxon GOUNDRY in central Burkina Faso. The ecological, 21 immunological, and reproductive differences among these taxa will critically impact 22 population responses to disease control strategies and environmental changes. Here we 23 2 examine whole-genome sequencing data from a longitudinal study of putative A. coluzzii in 24 western Burkina Faso. Surprisingly, many samples are genetically divergent from A. 25 coluzzii and all other Anopheles species and represent a new taxon, here designated 26 Anopheles TENGRELA (AT). Population genetic analysis suggests that GOUNDRY sensu 27 stricto represents an admixed population descended from both A. coluzzii and AT. AT 28 harbors low nucleotide diversity except for the 2La inversion polymorphism which is 29 maintained by overdominance. It shows numerous fixed differences with A. coluzzii 30 concentrated in several regions reflecting selective sweeps, but the two taxa are identical at 31 standard diagnostic loci used for taxon identification and thus AT may often go unnoticed. 32 We present an amplicon-based genotyping assay for identifying AT which could be usefully 33 applied to numerous existing samples. Misidentified cryptic taxa could seriously confound 34 ongoing studies of Anopheles ecology and evolution in western Africa, including phenotypic 35 and genotypic surveys of insecticide resistance. Reproductive barriers between cryptic 36 species may also complicate novel vector control efforts, for example gene drives, and 37 hinder predictions about evolutionary dynamics of Anopheles and Plasmodium. 38 39

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Mosquito microevolution drives Plasmodium falciparum dynamics

Cited by 23 publications

References 39 publications

JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

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

A population genomic unveiling of a new cryptic mosquito taxon within the malaria-transmittingAnopheles gambiaecomplex

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