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Flavivirus induces and antagonizes antiviral RNA interference in both mammals and mosquitoes

ABSTRACT: Flavivirus induces and antagonizes antiviral RNA interference in both mammals and mosquitoes

PROVIDER: PRJNA550985 | ENA |

REPOSITORIES: ENA

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Flavivirus induces and antagonizes antiviral RNA interference in both mammals and mosquitoes

Project description:Mosquito-borne flaviviruses maintain life cycles in mammals and mosquitoes. RNA interference (RNAi) has been demonstrated as an anti-flavivirus mechanism in mosquitoes; however, whether and how flavivirus induces and antagonizes RNAi-mediated antiviral immunity in mammals remains unknown. Here we showed that NS2A of Dengue virus-2 (DENV2) act as a viral suppressor of RNAi (VSR). When NS2A-mediated RNAi suppression was disabled, the resulting mutant DENV2 induced Dicer-dependent production of abundant DENV2-derived siRNAs in differentiated mammalian cells. Importantly, VSR-disabled DENV2 showed severe replication defects in mosquito and mammalian cells, and mice, which were rescued by the deficiency of RNAi. Moreover, NS2As of multiple flaviviruses act as VSRs in vitro and during viral infection in both organisms. Overall, our findings demonstrate that antiviral RNAi can be induced by flavivirus, while flavivirus uses NS2A as bona fide VSR to evade RNAi in mammals and mosquitoes, highlighting the importance of RNAi in flaviviral vector-host life cycles.

2020-02-24 | GSE133284 | GEO

Flavivirus induces and antagonizes antiviral RNA interference in both mammals and mosquitoes.

Project description: Not available

| S-EPMC7002134 | biostudies-literature

Cooler temperatures destabilize RNA interference and increase susceptibility of disease vector mosquitoes to viral infection

Project description:The impact of global climate change on the transmission dynamics of infectious diseases is the subject of extensive debate. The transmission of mosquito-borne viral diseases is particularly complex, with climatic variables directly affecting many parameters associated with the prevalence of disease vectors. While evidence shows that warmer temperatures often decrease the extrinsic incubation period of an arthropod-borne virus (arbovirus), exposure to cooler temperatures often predisposes disease vector mosquitoes to higher infection rates. RNA interference pathways are essential to antiviral immunity in the mosquito; however, few experiments have explored the effects of temperature on the RNAi machinery. Total small RNAs (miRNAs, siRNAs, piRNAs, etc.) were isolated and sequenced from the heads of sensor strain Aedes aegypti mosquitoes, or from the whole bodies of CHIKV-infected Aedes albopictus mosquitoes 8 hours post infection. Mosquitoes were grown at 18C or 28C in replicates of 1 (Ae. aegypti) or 3 (Ae. albopictus).

2013-08-13 | E-GEOD-46204 | biostudies-arrayexpress

A human blood-derived microRNA facilitates flavivirus infection in fed mosquitoes

Project description:A human blood-derived microRNA facilitates flavivirus infection in fed mosquitoes

| PRJNA704363 | ENA

TMEM41B is a pan-flavivirus host factor

Project description:Flaviviruses pose a constant threat to human health. These RNA viruses are transmitted by the bite of infected mosquitoes and ticks and regularly cause outbreaks. To identify host factors required for flavivirus infection we performed full-genome loss of function CRISPR-Cas9 screens. Based on these results we focused our efforts on characterizing the roles that TMEM41B and VMP1 play in the virus replication cycle. Our mechanistic studies on TMEM41B revealed that all members of the Flaviviridae family that we tested require TMEM41B. We tested 12 additional virus families and found that SARS-CoV-2 of the Coronaviridae also required TMEM41B for infection. Remarkably, single nucleotide polymorphisms (SNPs) present at nearly twenty percent in East Asian populations reduce flavivirus infection. Based on our mechanistic studies we propose that TMEM41B is recruited to flavivirus RNA replication complexes to facilitate membrane curvature, which creates a protected environment for viral genome replication.

2020-11-24 | GSE162040 | GEO

A human blood-derived microRNA facilitates flavivirus infection in fed mosquitoes [S0]

Project description:We report that the mosquito small RNA expression level in mosquitoes following a sugar meal

2022-05-01 | GSE180776 | GEO

A human blood-derived microRNA facilitates flavivirus infection in fed mosquitoes [S0]

Project description:A human blood-derived microRNA facilitates flavivirus infection in fed mosquitoes [S0]

| PRJNA749555 | ENA

A human blood-derived microRNA facilitates flavivirus infection in fed mosquitoes [miRNA-seq]

Project description:We report the human small RNA expression levels in mosquitoes following a blood meal

2022-05-01 | GSE167346 | GEO

The Hsf1-sHsp cascade has pan-antiviral activity in mosquitoes

Project description:Aedes mosquitoes transmit pathogenic arthropod-borne (arbo) viruses, putting nearly half the world’s population at risk. Blocking virus replication in mosquitoes rather than in humans serves as a promising approach to prevent arbovirus transmission, which requires in-depth knowledge of mosquito immunity. By integrating multi-omics data, we identified that heat shock factor 1 (Hsf1) regulates eight small heat shock protein (sHsp) genes within one topological associated domain. This Hsf1-sHsp cascade acts as an early response against chikungunya virus (CHIKV) infection and shows pan-antiviral activity in three vector mosquitoes, Aedes aegypti, Aedes albopictus, and Anopheles gambiae. We then assessed the baseline expression of sHsp genes in different tissues of female Ae. aegypti using RNA-seq, and we observed a highly dynamic expression pattern of sHsp genes that varied dramatically across different tissues. Interestingly, sHsp genes were expressed at low levels in two main barrier tissues, the midgut and salivary glands, compared to other tissues such as the crop. Importantly, activation of Hsf1 led to a reduced CHIKV infection rate in adult Ae. aegypti mosquitoes, demonstrating Hsf1 as a promising target for the development of novel intervention strategies to limit arbovirus transmission by mosquitoes.

2024-01-01 | GSE225070 | GEO

Cooler temperatures destabilize RNA interference and increase susceptibility of disease vector mosquitoes to viral infection

2013-08-13 | GSE46204 | GEO

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