Biology subjects

Kading, R. C.

Publications and source records attributed to Kading, R. C..

5 recordsLinked to original sources

bioRxiv2026

Detection of diverse coronaviruses, paramyxoviruses, and rhabdoviruses from cave-dwelling bats in Eastern Uganda

Bats harbor a diversity of viruses, some of which have the potential to impact human and livestock health. Caves in Eastern Uganda are commonly inhabited by bats in the genera Rhinolophus, Hipposideros, Myonycteris, and others. Human encroachment into these caves for shelter, hunting, mineral harvesting, and tourism poses a risk of exposure to infectious agents these bats may carry, yet little is known about the viruses present in these bats. From 2021 - 2023, 635 unique bats were captured in caves by mist net, with 69 bats resampled over the study for a total of 706 sampling instances. A total of 1,394 oral and rectal swabs were collected non-destructively and screened using molecular techniques for coronaviruses, paramyxoviruses, rhabdoviruses, flaviviruses, and filoviruses. Of these samples, 399 (56.5%) were collected during the rainy season and 307 (43.5%) during the dry season. Coronavirus RNA was detected in 59/706 (8.36%) of samples from Rhinolophus spp. (n = 35), Hipposideros caffer (n = 12), Myonycteris angolensis (n = 6), and Miniopterus spp. (n = 6). Six bats (0.85%) were positive for paramyxoviruses. Finally, (3 H. caffer, 1 M. angolensis, 1 Rhinolophus spp. and 1 Nycteris thebaica) 3 Rhinolophus bats were positive for rhabdoviruses (0.42%, all Rhinolophus spp.). No samples were positive for filovirus or flavivirus RNA. This project has generated novel data on the association of bat species and different viral strains present in these bats, advancing our knowledge of viral ecology and spillover risk at the human/bat interface.

genomics↗

bioRxiv2026

Mosquitoes of Macha: new mosquito species records from Macha and surrounding locations in southern Zambia with photographs

The biodiversity of mosquito taxa beyond Anopheles malaria vectors has been understudied in many parts of Africa. Here, we provide a new species record of mosquitoes from Macha and its surrounding locations in southern Zambia, as well as an updated list of species from the region. With the addition of 19 new species records in this region, the total list of mosquito species reported in Macha is now 46. We present high-resolution focus-stacked photographs of some of these species, many of which were only previously available as text or drawing descriptions in mosquito identification books and articles. We also include 34 COI sequences from Zambian mosquito species, five of which had no prior genetic information on Genbank. This visual guide as well as additional COI sequences provide essential tools for accurate mosquito surveillance in southern Zambia and establishes a baseline data for future invasive species monitoring.

zoology↗

bioRxiv2025

Altered histone modifications in Aedes aegypti following Rift Valley fever virus exposure

When arthropod-borne viruses (arboviruses) are delivered to vector mosquitoes in an infectious bloodmeal, viral components interact with host proteins to hijack cells and initiate replication. The extent to which arbovirus infection alters mosquito host transcriptional and genomic regulatory processes is currently unknown. We hypothesized that histone modifications would be altered in mosquitoes exposed to Rift Valley fever virus (RVFV MP12, Phlebovirus riftense, family Phleboviridae). We interrogated transcriptome and chromatin landscapes in Aedes aegypti midguts by performing Cleavage Under Targets and Release Using Nuclease (CUT&RUN), using H3K27ac and H3K9me3 marks. Altered H3K27ac marks were identified following RVFV MP12 exposure, as well as upon bloodfeeding alone. It took several days for differential H3K27ac marks to be associated with differentially expressed genes (DEGs) in RVFV-exposed midguts. H3K27ac peaks showed progressive depletion as infection progressed. Gene set enrichment analysis revealed that immune response transcripts were enriched at 1 and 3 dpf (days post-feeding) but depleted by 7 dpf. Hedgehog/Gli (glioma-associated oncogene homolog) signaling pathway transcripts were depleted, indicating possible viral manipulation of cellular polarization. Moreover, at 7 dpf, 7 of 102 DEGs were proximal to differentially acetylated sites in a pattern expected to favor viral propagation. However, one transcript coding for an antiviral effector (LysM-TLDc domain protein) showed significant depletion of both H3K9me3 and H3K27ac marks. Analysis of midguts after a non-infectious bloodmeal versus sugar-fed controls revealed global changes to H3K27ac and H3K9me3 marks during and following the period of bloodmeal digestion. Differential H3K27ac marks were proximal to one quarter of all DEGs at 1 dpf, consistent with an important role of H3K27ac in bloodmeal digestion. These results demonstrate that H3K27ac and H3K9me3 patterns are altered upon virus exposure in a complex interplay that favors viral replication but is also countered by host responses to limit replication. Author SummaryMosquito-borne viruses produce a high disease burden across the globe. Though transgenic mosquitoes are being developed to help mitigate disease transmission, little is known of the ways in which arbovirus infection alters chromatin structure in mosquitoes. Arboviruses typically replicate and assemble on cytoplasmic membranes and have not been traditionally expected to alter processes in the nucleus. Some histone post-translational modifications, such as, e.g. histone 3 lysine 27 acetylation (H3K27ac), are associated with accessible chromatin regions, whereas others, e.g, histone 3 lysine 9 triple-methylation (H3K9me3), are associated with inaccessible chromatin. This work explores these chromatin modifications and the ways in which they are tied to gene expression changes. Multiple lines of evidence presented here support the hypothesis that H3K27ac levels change in RVFV-exposed mosquitoes and are associated with altered gene expression in a manner consistent with viral hijacking of gene expression in the nucleus. In addition, bloodfeeding alone also altered H3K27ac levels at 1-day post-feeding, and over one quarter of differentially expressed genes had changes to H3K27ac marks near transcription start sites, which is consistent with the idea that broad metabolic changes occur to support digestion and egg development.

genomics↗

bioRxiv2022

On the origin and evolution of the mosquito male-determining factor Nix

The mosquito family Culicidae is divided into two subfamilies named the Culicinae and Anophelinae. Nix, the dominant male-determining factor, has only been found in the culicines Aedes aegypti and Ae. albopictus, two important arboviral vectors that belong to the subgenus Stegomyia. Here we performed sex-specific whole-genome sequencing and RNAseq of divergent mosquito species and explored additional male-inclusive datasets to investigate the distribution of Nix. Except for the Culex genus, Nix homologs were found in all species surveyed from the Culicinae subfamily, including 12 additional species from three highly divergent tribes comprising 4 genera, suggesting Nix originated at least 133-165 MYA. Heterologous expression of one of three divergent Nix ORFs in Ae. aegypti resulted in partial masculinization of genetic females as evidenced by morphology and doublesex splicing. It is not clear whether insufficient transgene expression or sequence divergence or both are responsible for the lack of phenotype for the other two. Phylogenetic analysis suggests Nix is related to femaleless (fle), a recently described intermediate sex-determining factor found exclusively in anopheline mosquitoes. Nix from all species has a conserved structure, including three RNA-recognition motifs (RRMs), as does fle. However, Nix has evolved at a much faster rate than fle. The RRM3 of both Nix and fle are related to the single RRM of a widely distributed and conserved splicing factor transformer-2 (tra2). RRM3-based phylogenetic analysis suggests this domain in Nix and fle may have evolved from tra2 in a common ancestor of mosquitoes. Our results provide insights into the evolution of sex-determination and homomorphic sex chromosomes in mosquitoes, and will inform broad applications of mosquito-control strategies based on manipulating sex ratios towards the non-biting males.

evolutionary biology↗

bioRxiv2021

A novel glucocorticoid and androgen receptor modulator reduces viral entry and innate immune inflammatory responses in the Syrian Hamster model of SARS-CoV-2

Since its initial discovery in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID19, has spread worldwide and despite significant research efforts, treatment options remain limited. Replication of SARS-CoV-2 in lung is associated with marked infiltration of macrophages and activation of innate immune inflammatory responses triggered, in part, by heightened production of interleukin-6 (IL-6) that recruits lymphocytes to the site of infection that amplify tissue injury. Antagonists of the glucocorticoid and androgen receptors have shown promise in experimental models of COVID19 and in clinical studies, because cell surface proteins required for viral entry, angiotensin converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2), are transcriptionally regulated by these receptors. We therefore postulated that the glucocorticoid (GR) and androgen receptor (AR) antagonist, PT150, would reduce infectivity of SARS-CoV-2 and prevent inflammatory lung injury in the Syrian golden hamster model of COVID19. Animals were infected intranasally with 2.5 x 104 TCID50/ml equivalents of SARS-CoV-2 (strain 2019-nCoV/USA-WA1/ 2020) and PT150 was administered by oral gavage at 30 and 100 mg/Kg/day for a total of 7 days. Animals were then examined at days 3, 5 and 7 post-infection (DPI) for lung histopathology, viral load and production of proteins regulating the initiation and progression of SARS-CoV-2 infection. Results of these studies indicated that oral administration of PT150 decreased replication of SARS-CoV-2 in lung, as well as expression of ACE2 and TMPRSS2 protein. Hypercellularity and inflammatory cell infiltration driven by macrophage responses were dramatically decreased in PT150-treated animals, as was tissue damage and expression of IL-6. Molecular modeling suggested that PT150 binds to the co-activator interface of the ligand binding domain of both AR and GR and thereby acts as an allosteric modulator and transcriptional repressor of these receptors. Phylogenetic analysis of AR and GR across multiple species permissive to SARS-CoV-2 infection revealed a high degree of sequence identity maintained across species, including human, suggesting that the mechanism of action and therapeutic efficacy observed in Syrian hamsters would likely be predictive of positive outcomes in patients. PT150 is therefore a strong candidate for further clinical development for the treatment of COVID19 across variants of SARS-CoV-2.

immunology↗