Biology subjects

Bennouna, D.

Publications and source records attributed to Bennouna, D..

3 recordsLinked to original sources

bioRxiv2026

Metabolite profiles distinguish exposure to Dengue and Zika flaviviruses in human induced pluripotent stem cells (hiPSCs)

Flaviviruses such as Dengue virus (DENV), Zika virus (ZIKV) and West Nile Virus (WNV) pose growing public health threats, exacerbated by asymptomatic infections and non-vector transmission. Current diagnostics, including nucleic acid tests and serology, are limited by transient viremia and antibody cross-reactivity, underscoring the need for improved detection methods. We utilized untargeted metabolomics to differentiate DENV and ZIKV infections in human induced pluripotent stem cells (hiPSCs), a model relevant to study virus-host interactions, drug screening, and therapeutic safety. LC-MSbased profiling revealed virus-specific metabolic reprogramming during both acute and long-term infections. DENV3 induced early and sustained activation of metabolic features, while ZIKV-MR766 triggered transient suppression. Long term infection with DENV2, DENV3, or ZIKV-PRV resulted in distinct metabolic signatures in hiPSCs, with ZIKV-PRV showing the greatest divergence. Shared metabolite changes across conditions included amino acids (e.g., tryptophan, glutamate), lipids, and nucleosides. Functional studies demonstrated that tryptophan metabolism regulates infection dynamics: inhibiting serotonin biosynthesis reduced viral load, whereas blocking kynurenine synthesis enhanced viral replication. These findings position metabolomics as a viable approach for flavivirus detection and highlight metabolic pathways as potential therapeutic targets. ImportanceAccurate diagnosis of flavivirus infections remains challenging due to short periods of viremia, high rates of asymptomatic infection, and extensive serologic cross-reactivity among related viruses such as DENV and ZIKV. These limitations complicate clinical diagnosis, surveillance, and screening of human donor tissues. In this study, we demonstrate that untargeted metabolomics can distinguish ZIKV and DENV infections by identifying virus-specific host metabolic signatures during both acute and long-term infection. Using human induced pluripotent stem cells as a clinically relevant model, we show that metabolic reprogramming persists even in the absence of overt cytopathic effects and can reveal functional pathways that regulate viral replication. Our findings highlight host metabolite profiling as a complementary diagnostic strategy that may improve detection of flavivirus exposure, particularly in asymptomatic individuals or settings where conventional molecular and serologic tests are insufficient.

microbiology↗

bioRxiv2025

Estrogen Signaling During Abrupt Involution Leads to Long-Term Metabolic Dysfunction Similar to Estrogen Receptor Negative Breast Cancer

Epidemiological data links lack of breastfeeding with increased risk of breast cancer. Breast tissue undergoes remodeling to pre-pregnancy state after birth through involution. Long-term breastfeeding leads to gradual involution (GI). Lack of breastfeeding leads to abrupt involution (AI). While estrogen impacts repopulation of adipocytes, AI causes several precancerous changes in the mouse mammary gland. The impact of AI on adipocyte repopulation and metabolism is yet to be elucidated. ObjectivesTo investigate effects of AI on mammary gland metabolism and its potential link to breast cancer. MethodsAt partum (day 0), FVB/n dams were randomized to AI or GI and standardized to 6 pups. AI mice had pups removed on day 7 postpartum to mimic short-term breastfeeding. GI mice had 3 pups each were removed on day 28 and 31 postpartum to mimic gradual weaning. Mammary glands were harvested on day 28, 56, and 120 postpartum. Subset of AI mice had long-term sustained release tamoxifen placed subscapular on day 8 postpartum. Metabolic changes were assessed using: 1) transcriptional; 2) functional; 3) oxidative stress; and 4) metabolites analysis. ResultsDay 28 GI glands sustains/continues milk synthesis pathways impacting metabolic comparison with day28 AI glands. Day 28 AI when compared to day 56 GI showed upregulation of estrogen signaling, neutrophil degranulation, glucose metabolism, RNA synthesis, and down regulation of adipogenesis and glycolysis. At day 120, AI glands had downregulation of oxidative phosphorylation and upregulation of mitochondria dysfunction similar to pregnancy associated estrogen receptor negative breast cancer. Tamoxifen treatment of AI dams showed metabolic pathways and estrogen signaling similar to that of GI glands on day 28. ConclusionEarly metabolic phenotypes in AI and GI glands may be caused by differences in adipocyte repopulation related to estrogen signaling. Long-term metabolic effects of AI lead to similar metabolic effects found in breast cancer.

cancer biology↗

bioRxiv2020

A novel family of secreted proteins linked to plant gall development

In an elaborate form of inter-species exploitation, many insects hijack plant development to induce novel plant organs called galls that provide the insect with a source of nutrition and a temporary home. Galls result from dramatic reprogramming of plant cell biology driven by insect molecules, but the roles of specific insect molecules in gall development have not yet been determined. Here we study the aphid Hormaphis cornu, which makes distinctive "cone" galls on leaves of witch hazel Hamamelis virginiana. We found that derived genetic variants in the aphid gene determinant of gall color (dgc) are associated with strong downregulation of dgc transcription in aphid salivary glands, upregulation in galls of seven genes involved in anthocyanin synthesis, and deposition of two red anthocyanins in galls. We hypothesize that aphids inject DGC protein into galls, and that this results in differential expression of a small number of plant genes. Dgc is a member of a large, diverse family of novel predicted secreted proteins characterized by a pair of widely spaced cysteine-tyrosine-cysteine (CYC) residues, which we named BICYCLE proteins. Bicycle genes are most strongly expressed in the salivary glands specifically of galling aphid generations, suggesting that they may regulate many aspects of gall development. Bicycle genes have experienced unusually frequent diversifying selection, consistent with their potential role controlling gall development in a molecular arms race between aphids and their host plants. One Sentence SummaryAphid bicycle genes, which encode diverse secreted proteins, contribute to plant gall development.

genetics↗