Biology subjects

Quinones, A.

Publications and source records attributed to Quinones, A..

4 recordsLinked to original sources

bioRxiv2024

Expression of Intron-containing HIV-1 RNA Induces NLRP1 Inflammasome Activation in Myeloid Cells

Despite the success of antiretroviral therapy (ART) in suppressing plasma viremia in people living with human immunodeficiency virus type-1 (HIV-1), persistent viral RNA expression in tissue reservoirs is observed and can contribute to HIV-1-induced immunopathology and comorbidities. Infection of long-lived innate immune cells, such as tissue-resident macrophages and microglia may contribute to persistent viral RNA production and chronic inflammation. We recently reported that de-novo cytoplasmic expression of HIV-1 intron-containing RNA (icRNA) in macrophages and microglia leads to MDA5 and MAVS-dependent innate immune sensing and induction of type I IFN responses, demonstrating that HIV icRNA is a pathogen-associated molecular pattern (PAMP). In this report, we show that cytoplasmic expression of HIV-1 icRNA also induces NLRP1 inflammasome activation and IL-1{beta} secretion in macrophages and microglia in a RLR- and endosomal TLR-independent manner. Infection of both macrophages and microglia with either replication-competent or single-cycle HIV-1 induced IL-1{beta} secretion, which was attenuated when cytoplasmic expression of viral icRNA was prevented. While IL-1{beta} secretion was blocked by treatment with caspase-1 inhibitors or knockdown of NLRP1 or caspase-1 expression in HIV- infected macrophages, overexpression of NLRP1 significantly enhanced IL-1{beta} secretion in an HIV-icRNA-dependent manner. Immunoprecipitation analysis revealed interaction of HIV-1 icRNA, but not multiply-spliced HIV-1 RNA, with NLRP1, suggesting that HIV-1 icRNA sensing by NLRP1 is sufficient to trigger inflammasome activation. Together, these findings reveal a pathway of NLRP1 inflammasome activation induced by de novo expressed HIV icRNA in HIV- infected myeloid cells.

microbiology↗

bioRxiv2024

Macrophage-intrinsic MDA5-IRF5 axis drives HIV-1 icRNA-induced inflammatory responses

Despite effective antiretroviral therapy (ART), transcriptionally competent HIV-1 reservoirs persist and contribute to persistent immune activation in people living with HIV (PWH). HIV-1-infected macrophages are important mediators of chronic innate immune activation, though mechanisms remain unclear. We previously reported that nuclear export and cytoplasmic expression of HIV-1 intron-containing RNA (icRNA) activates mitochondrial antiviral signaling protein (MAVS)-mediated type I interferon (IFN) responses in macrophages. In this study, we demonstrate an essential role of melanoma differentiation-associated protein 5 (MDA5) in sensing HIV-1 icRNA and promoting MAVS-dependent IRF5 activation in macrophages. Suppression of MDA5, but not RIG-I expression nor disruption of endosomal TLR pathway, abrogated HIV-1 icRNA-induced type I IFN responses and IP-10 expression in macrophages. Furthermore, induction of IP-10 in macrophages upon HIV-1 icRNA sensing by MDA5 was uniquely dependent on IRF5. Additionally, monocytes and MDMs from older (>50 years) individuals exhibit constitutively higher levels of IRF5 expression compared to younger (<35 years) individuals, and HIV-1 icRNA induced IP-10 expression was significantly enhanced in older macrophages, which was attenuated upon ablation of IRF5 expression suggesting that IRF5 functions as a major mediator of pro-inflammatory response downstream of MDA5-dependent HIV-1 icRNA sensing, dysregulation of which might contribute to chronic inflammation in older PWH.

microbiology↗

bioRxiv2023

An RGB based deep neural network for high fidelity Fusarium head blight phenotyping in wheat

Fusarium head blight (FHB) in wheat is an economically important disease, which can cause yield losses exceeding 50% and the causal pathogen that infects spikes produces harmful mycotoxins. Breeding for host resistance remains the most effective disease control method; but time, labor, and human subjectivity during disease scoring limits selection advancements. In this study we describe an innovative, high-throughput phenotyping rover for capturing in-field RGB images and a deep neural network pipeline for wheat spike detection and FHB disease quantification. The image analysis pipeline successfully detects wheat spikes from images under variable field conditions, segments spikes and diseased tissue in the spikes, and quantifies disease severity as the region of intersection between spike and disease masks. Model inferences on an individual spike and plot basis were compared to human visual disease scoring in the field and on imagery for model evaluation. The precision and throughput of the model surpassed traditional field rating methods. The accuracy of FHB severity assessments of the model was equivalent to human disease annotations of images, however individual spike disease assessment was influenced by field location. The model was able to quantify FHB in images taken with different camera orientations in an unseen year, which demonstrates strong generalizability. This innovative pipeline represents a breakthrough in FHB phenotyping, offering precise and efficient assessment of FHB on both individual spikes and plot aggregates. The model is robust to different conditions and the potential to standardize disease evaluation methods across the community make it a valuable tool for studying and managing this economically significant fungal disease.

plant biology↗

bioRxiv2022

SELF PRUNING 3C is a flowering repressor that modulates seed germination, root architecture and drought responses

Allelic variation in the CETS (CENTRORADIALIS, TERMINAL FLOWER 1, SELF PRUNING) gene family has been shown to control agronomically important traits in many crops. CETS genes encode phosphatidylethanolamine binding proteins (PEBPs) that have a central role in flowering time control as florigenic and anti-florigenic signals. The great expansion of CETS genes in many species suggests that the functions of this family go beyond flowering. Here, we characterize the tomato SELF PRUNING 3C (SP3C) gene, and show that besides acting as a flowering repressor it also regulates seed germination and modulates root architecture. We show that loss of SP3C function in CRISPR/Cas9-generated mutant lines accelerates seed germination and increases root length with lower root side branching. Higher SP3C expression in transgenic lines promotes the opposite effects and also improves tolerance to water stress in seedlings. These discoveries provide insights into the role of SP paralogs in agronomically relevant traits and support future exploration of the involvement of CETS genes in abiotic stress responses. HighlightThe SELF PRUNING 3C (SP3C) gene is a repressor of flowering in tomato and exhibits additional functions, acting as a repressor of seed germination and modulating root architecture.

molecular biology↗