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Sodeinde, A.

Publications and source records attributed to Sodeinde, A..

5 recordsLinked to original sources

Heterogeneity in inhibition of genetically diverse dengue virus strains by Wolbachia

The release of Aedes aegypti mosquitoes transinfected with the virus-inhibiting Wolbachia bacterium has the potential to reduce the burden caused by dengue virus (DENV). However, the robustness of this control strategy across the wide genetic diversity of DENV remains unknown. Here, we systematically tested two commonly used Wolbachia strains (wAlbB and wMelM) for their ability to inhibit 60 genetically diverse DENV isolates spanning all four serotypes. We found stronger inhibition by wMelM (median relative dissemination: 0.04) than wAlbB (median relative dissemination: 0.19). Furthermore, while we found substantial heterogeneity in inhibition across DENV isolates, we found that more DENV-3 isolates were weakly inhibited (median relative dissemination: 0.47 for wAlbB and 0.39 for wMelM) compared to the other serotypes (median relative disseminations: 0.10-0.18 for wAlbB and 0-0.11 for wMelM). Using transmission dynamic models, we further showed that differential Wolbachia inhibition results in increased probability of reemergence, particularly in high transmission intensity settings, with strong selection for DENV strains that have higher relative dissemination in mosquitoes. Our work highlights the importance of considering DENV genetic diversity, including the long-term risk of selection, in Wolbachia-based control interventions.

microbiology↗

Implications of successive blood feeding on Wolbachia-mediated dengue virus inhibition in Aedes aegypti mosquitoes

Dengue virus (DENV) is a mosquito-borne virus that poses a continued and increasing threat to public health. A promising strategy to mitigate the burden of DENV is introgression of the virus-inhibiting Wolbachia pipientis bacterium into Aedes aegypti populations in the field. While previous studies on Wolbachia-mediated virus inhibition have typically assessed viral replication following a single bloodmeal, the main vector of DENV, Ae. aegypti, feeds frequently, often biting multiple hosts per gonotrophic cycle and promptly attempting to refeed following egg laying. Previously, we demonstrated that successive blood feeding reduces the extrinsic incubation period (EIP) and shortens the time it takes for a mosquito to be able to transmit viruses to a new host. With this in mind, we investigated the impact of successive blood meals on DENV serotype 2 (DENV-2) in Ae. aegypti in the presence or absence of Wolbachia (wAlbB and wMelM). We found that both WT and Wolbachia transinfected had increased DENV-2 dissemination 7 days post-infection as well as higher body titers of DENV-2 in the double-fed groups. Using these empirical data in a binomial regression model, we estimated that successive feeding increased the probability of WT and Wolbachia transinfected mosquitoes surviving the EIP. When we estimated the odds of surviving the EIP for mosquitoes with Wolbachia relative to WT mosquitoes, successive feeding increased the chances of WT mosquitoes surviving the EIP more than in mosquitoes with Wolbachia, indicating a strong inhibitory effect of Wolbachia even in the context of natural frequent blood feeding behavior. Our work shows that mosquito feeding behavior should be considered when assessing the inhibitory effects of Wolbachia on DENV.

microbiology↗

Survey of white-footed mice in Connecticut, USA reveals low SARS-CoV-2 seroprevalence and infection with divergent betacoronaviruses

Diverse mammalian species display susceptibility to and infection with SARS-CoV-2. Potential SARS-CoV-2 spillback into rodents is understudied despite their host role for numerous zoonoses and human proximity. We assessed exposure and infection among white-footed mice (Peromyscus leucopus) in Connecticut, USA. We observed 1% (6/540) wild-type neutralizing antibody seroprevalence among 2020-2022 residential mice with no cross-neutralization of variants. We detected no SARS-CoV-2 infections via RT-qPCR, but identified non-SARS-CoV-2 betacoronavirus infections via pan-coronavirus PCR among 1% (5/468) of residential mice. Sequencing revealed two divergent betacoronaviruses, preliminarily named Peromyscus coronavirus-1 and -2. Both belong to the Betacoronavirus 1 species and are [~]90% identical to the closest known relative, Porcine hemagglutinating encephalomyelitis virus. Low SARS-CoV-2 seroprevalence suggests white-footed mice may not be sufficiently susceptible or exposed to SARS-CoV-2 to present a long-term human health risk. However, the discovery of divergent, non-SARS-CoV-2 betacoronaviruses expands the diversity of known rodent coronaviruses and further investigation is required to understand their transmission extent.

ecology↗

Spd-2 Gene Duplication Suggests Cell-Type Specific Assembly Mechanisms of Pericentriolar Material

Centrosomes are multi-protein complexes that function as the major microtubule organizing center (MTOC) for the cell. While centrosomes play tissue-specific MTOC functions, little is known about how particular centrosome proteins are regulated across cell types to achieve these different functions. To investigate this cell type-specific diversity, we searched for gene duplications of centrosome genes in the Drosophila lineage with the aim of identifying centrosome gene duplications where each copy evolved for specialized functions. Through in depth functional analysis of a Spd-2 gene duplication in the Willistoni group, we discovered differences in the regulation of PCM in somatic and male germline cells. The parental gene, Spd-2A, is expressed in somatic cells, where it can function to organize pericentriolar material (PCM) and the mitotic spindle in larval brain neuroblasts. Spd-2A is absent during male meiosis, and even when ectopically expressed in spermatocytes it fails to rescue PCM and spindle organization. In contrast, the new gene duplicate, Spd-2B, is expressed specifically in spermatocytes. During male meiosis, Spd-2B localizes to centrosomes, organizes PCM and spindles, and is sufficient for proper male fertility. Experiments using chimeric transgenes reveal that differences in the C-terminal tails of Spd-2A and Spd-2B are responsible for these functional changes. Thus, Spd-2A and Spd-2B have evolved complementary functions by specializing for distinct subsets of cells. Together, our results demonstrate that somatic cells and male germline cells have fundamentally different requirements for PCM, suggesting that PCM proteins such as Spd-2 is differentially regulated across cell types to satisfy distinct requirements. HighlightsO_LISpd-2 gene duplication in the Willistoni group is rapidly evolving C_LIO_LIParent gene Spd-2A is expressed in somatic cells, whereas the gene duplicate Spd-2B is expressed in spermatocytes C_LIO_LISpd-2A organizes pericentriolar material during somatic cell mitosis C_LIO_LISpd-2B is specialized for pericentriolar material organization during male meiosis C_LI

cell biology↗

Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races

Host antiviral proteins engage in evolutionary arms races with viruses, in which both sides rapidly evolve at interaction interfaces to gain or evade immune defense. For example, primate TRIM5 uses its rapidly evolving "v1" loop to bind retroviral capsids, and single mutations in this loop can dramatically improve retroviral restriction. However, it is unknown whether such gains of viral restriction are rare, or if they incur loss of pre-existing function against other viruses. Using deep mutational scanning, we comprehensively measured how single mutations in the TRIM5 v1 loop affect restriction of divergent retroviruses. Unexpectedly, we found that the majority of mutations increase antiviral function. Moreover, most random mutations do not disrupt potent viral restriction, even when it is newly acquired via single adaptive substitutions. Our results indicate that TRIM5s adaptive landscape is remarkably broad and mutationally resilient, maximizing its chances of success in evolutionary arms races with retroviruses.

evolutionary biology↗