Bishop, C. R. | Search bioRxiv

bioRxiv2022

Analysis of Aedes aegypti microRNAs in response to Wolbachia wAlbB infection and their potential role in mosquito longevity

The mosquito Aedes aegypti is the primary vector of a range of medically important viruses including dengue, Zika, West Nile, yellow fever, and chikungunya viruses. The endosymbiotic bacterium Wolbachia pipientis wAlbB strain is a promising biocontrol agent for blocking viral transmission by Ae. aegypti. To predict the long-term efficacy of field applications, a thorough understanding of the interactions between symbiont, host, and pathogen is required. Wolbachia influence host physiology in a variety of ways including reproduction, immunity, metabolism, and longevity. MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that regulate gene expression in eukaryotes and viruses. A number of miRNAs are known to regulate biological processes in Drosophila and mosquitoes, including facilitating Wolbachia maintenance. We generated the first chromosomal map of Ae. aegypti miRNAs, and compared miRNA expression profiles between a wAlbB-transinfected Ae. aegypti mosquito line and a tetracycline cleared derivative, using deep small RNA-sequencing. We found limited modulation of miRNAs in response to wAlbB infection. Several miRNAs were modulated in response to age, some of which showed greater upregulation in wAlbB-infected mosquitos than in tetracycline cleared ones. By selectively inhibiting some differentially expressed miRNAs, we identified miR-2946-3p and miR-317-3p as effecting mosquito longevity. ImportanceWolbachia is an endosymbiotic bacterium found in about 65% of insect species. It is mostly known for reproductive manipulations of the host, and also blocking replication of positive sense RNA viruses. Transinfection of Wolbachia into Aedes aegypti mosquitoes, which transmit a variety of arboviruses, including dengue virus, has provided a novel biological approach in reducing transmission of arboviruses. To gain a better understanding of Wolbachia-mosquito interactions, we investigated the impact of Wolbachia on the microRNA profile of Ae. aegypti mosquitoes. We produced the first chromosome-level map of Ae. Aegypti miRNAs. We found modulation of microRNAs in mosquitoes due to age, with two miRNAs, 317-3p and 2946-3p, showing significant increase with age. Inhibition of 317-3p and 2946-3p led to reduced mosquito life span in wAlbB-infected mosquitoes. The outcomes provide insights into underlying molecular mechanisms involved in Wolbachia-host interactions.

microbiology↗

bioRxiv2022

Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression

BACKGROUNDHow well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. The K18-hACE2 mouse model has been widely used for evaluation of new interventions for COVID-19. METHODHerein we use RNA-Seq data and bioinformatics approaches to compare the transcriptional responses in the SARS-CoV-2 infected lungs of K18-hACE2 mice with those seen in humans. RESULTSOverlap in differentially expressed genes was generally poor ({approx}20-30%), even when multiple studies were combined. The overlap was not substantially improved when a second mouse model was examined wherein hACE was expressed from the mouse ACE2 promoter. In contrast, analyses of immune signatures and inflammatory pathways illustrated highly significant concordances between the species. CONCLUSIONAs immunity and immunopathology are the focus of most studies, these hACE2 transgenic mouse models can thus be viewed as representative and relevant models of COVID-19.

molecular biology↗

bioRxiv2021

Microplastic consumption induces inflammatory signatures in the colon and prolongs a viral arthritis

Global microplastic (MP) contamination and the effects on the environment are well described. However, the potential for MP consumption to affect human health remains controversial. Mice consuming {approx}80 {micro}g/kg/day of 1 {micro}m polystyrene MPs via their drinking water for a month showed no weight loss, nor were MPs detected in organs. The microbiome was also unchanged. MP consumption did lead to small transcriptional changes in the colon suggesting plasma membrane perturbations and mild inflammation. Mice were challenged with the arthritogenic chikungunya virus, with MP consumption leading to a significantly prolonged arthritic foot swelling that was associated with elevated Th1, NK cell and neutrophil signatures. Immunohistochemistry also showed a significant increase in the ratio of neutrophils to monocyte/macrophages. The picture that emerges is reminiscent of enteropathic arthritis, whereby perturbations in the colon are thought to activate innate lymphoid cells that can inter alia migrate to joint tissues to promote inflammation.

immunology↗