Rift Valley Fever Virus Primes Immune Responses in Aedes aegypti Cells

Lauréti, Mathilde; Lee, Rui-Xue; Bennett, Amelia; Wilson, Lucas Aladar; Sy, Victoria Elena; Kohl, Alain; Dietrich, Isabelle

doi:10.3390/pathogens12040563

Cited by 6 publications

(5 citation statements)

References 93 publications

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“…This finding differed from studies performed in human cells with CHIKV (Li et al, 2012) and mosquito cells with DENV (Anglero-Rodrıǵuez et al, 2021) where 1 h of poly(I:C) priming was sufficient to reduce virus replication. However, we did observe the (Laureti et al, 2023). It may thus be worthwhile to measure AMP expression after poly(I:C) treatment and virus infection to determine if a similar priming effect is observed when a viral PAMP is used prior to a virus infection.…”

Section: Discussionmentioning

confidence: 72%

“…quinquefasciatus mosquitoes at varying timepoints would help identify additional factors that may be involved in an antiviral response. It has also been shown that priming Aag2 cells with Rift Valley fever virus results in higher AMP expression after bacterial challenge than virus infection or bacterial challenge alone ( Laureti et al., 2023 ). It may thus be worthwhile to measure AMP expression after poly(I:C) treatment and virus infection to determine if a similar priming effect is observed when a viral PAMP is used prior to a virus infection.…”

Section: Discussionmentioning

confidence: 99%

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Elucidating the role of dsRNA sensing and Toll6 in antiviral responses of Culex quinquefasciatus cells

Prince,

Chan,

Rückert

2023

Front. Cell. Infect. Microbiol.

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The first step of any immune response is the recognition of foreign molecular structures inside the host organism. An important molecule that is generally foreign to eukaryotic cells is long double-stranded RNA (dsRNA), which can be generated during virus replication. The mechanisms of sensing viral dsRNA are well-studied in mammalian systems but are only poorly understood in insects, including disease vectors such as Culex quinquefasciatus mosquitoes. These mosquitoes are vectors for important arboviruses, such as West Nile virus, and Culex species mosquitoes are distributed across the globe in many temperate and tropical regions. The major antiviral response triggered by dsRNA in mosquitoes is RNA interference – a sequence-specific response which targets complementary viral RNA for degradation. However, here, we aimed to identify whether sequence-independent dsRNA sensing, mimicked by poly(I:C), can elicit an antiviral response. We observed a significant reduction in replication of La Crosse virus (LACV) in Cx. quinquefasciatus mosquito cells following poly(I:C) priming. We identified a number of antimicrobial peptides and Toll receptors that were upregulated at the transcript level by poly(I:C) stimulation. Notably, Toll6 was upregulated and we determined that a knockdown of Toll6 expression resulted also in increased LACV replication. Future efforts require genetic tools to validate whether the observed Toll6 antiviral activity is indeed linked to dsRNA sensing. However, large-scale functional genomic and proteomic approaches are also required to determine which downstream responses are part of the poly(I:C) elicited antiviral response.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Elucidating the role of dsRNA sensing and Toll6 in antiviral responses of Culex quinquefasciatus cells

Prince,

Chan,

Rückert

2023

Front. Cell. Infect. Microbiol.

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“…In line with this, a recent paper showed that the RVFV infection of Ae. aegypti Aag2 cells can prime immune responses, resulting in increased expression of certain bacterial PRRs and an enhanced response to bacterial challenge [74]. These data indicate that RVFV infection is indeed sensed by the mosquito immune system, resulting in increased IMD pathway sensitivity.…”

Section: The Imd Pathwaymentioning

confidence: 84%

Recognition of Arboviruses by the Mosquito Immune System

et al. 2023

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Arthropod-borne viruses (arboviruses) pose a significant threat to both human and animal health worldwide. These viruses are transmitted through the bites of mosquitoes, ticks, sandflies, or biting midges to humans or animals. In humans, arbovirus infection often results in mild flu-like symptoms, but severe disease and death also occur. There are few vaccines available, so control efforts focus on the mosquito population and virus transmission control. One area of research that may enable the development of new strategies to control arbovirus transmission is the field of vector immunology. Arthropod vectors, such as mosquitoes, have coevolved with arboviruses, resulting in a balance of virus replication and vector immune responses. If this balance were disrupted, virus transmission would likely be reduced, either through reduced replication, or even through enhanced replication, resulting in mosquito mortality. The first step in mounting any immune response is to recognize the presence of an invading pathogen. Recent research advances have been made to tease apart the mechanisms of arbovirus detection by mosquitoes. Here, we summarize what is known about arbovirus recognition by the mosquito immune system, try to generate a comprehensive picture, and highlight where there are still gaps in our current understanding.

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“…To this end, we stimulated mosquito cells with heat-inactivated (HI) E. coli, which is known to result in robust induction of antimicrobial gene expression (35,36). We collected chromatin samples for PROseq at one and four hours post immune challenge (Fig.…”

Section: Dynamic Control Of Host Responses To Bacterial Stimulationmentioning

confidence: 99%

Characterization of gene regulatory elements and dynamic antimicrobial immune responses in mosquito cells using PRO-seq

van Hout,

Himanen,

Vihervaara

et al. 2023

Preprint

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TheAedes aegyptimosquito transmits arboviruses such as dengue, Zika, and chikungunya virus, posing a substantial threat to global health. The mosquito immune response determines virus transmission, yet, insight into the transcriptional regulation of mosquito immunity remains limited. In this study, we optimized the nascent RNA-sequencing method Precision Run-On sequencing (PRO-seq) forAedes aegyptiAag2 cells. PRO-seq enabled profiling the distribution of active RNA polymerases across the mosquito genome at nucleotide precision and identified the exact transcription start nucleotides (TSN) of expressed genes. Based on exact positioning of the TSN, we uncovered core promoter elements, including the Initiator and Downstream Promoter Elements. Notably, RNA polymerase accumulates at the promoter-proximal region of genes, but transcribes into the divergent region to a lesser extent than in vertebrates. To investigate rapid and dynamic immune responses, Aag2 cells were immune-stimulated with heat-inactivatedE. colifor 1 and 4 hours. Differential gene expression analysis revealed different groups of genes to be induced over time. While Clip domain serine proteases and antimicrobial peptides were induced promptly and sustained, a delayed stress response consisting of heat shock-related genes was only seen at 4 hours after stimulation. Strikingly, gene sets with different temporal expression profiles were associated with distinct transcription factor binding motifs. Altogether, our study provides valuable insights into the functional genomics ofAedes aegyptiand indicates that even within a rapid response, different dynamics emerge, potentially regulated by distinct transcription factors. These insights are crucial to gain a better understanding of the mosquito immune response and its regulation.

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Rift Valley Fever Virus Primes Immune Responses in Aedes aegypti Cells

Cited by 6 publications

References 93 publications

Elucidating the role of dsRNA sensing and Toll6 in antiviral responses of Culex quinquefasciatus cells

Elucidating the role of dsRNA sensing and Toll6 in antiviral responses of Culex quinquefasciatus cells

Recognition of Arboviruses by the Mosquito Immune System

Characterization of gene regulatory elements and dynamic antimicrobial immune responses in mosquito cells using PRO-seq

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