Biology subjects

MONTOYA, M.

Publications and source records attributed to MONTOYA, M..

2 recordsLinked to original sources

bioRxiv2026

A single Omicron mutation reshapes ORF3a-driven host-cell remodelling

SARS-CoV-2 ORF3a remodels host membranes, but the structural basis and metabolic consequences of this process remain unclear. Here, we combine complementary imaging approaches to define ORF3a function at nanometric scale, identifying underlying mechanisms, and determining how Omicron variant rewire this activity. ORF3a from the ancestral Wuhan strain disrupts Golgi cisternae, drives the formation of ORF3a dense vesicles, remodels mitochondrial architecture, and promotes lipid droplet expansion. Multi-omics analyses further reveal selective triacylglycerol accumulation linked to DGAT1 upregulation, which we validate pharmacologically through DGAT1 inhibition. In contrast, Omicron ORF3a variant, despite carrying only the Thr223Ile substitution within the {beta}7-{beta}8 loop at the bottom of the cytosolic domain, induced a dramatic phenotypic shift: ORF3a localizes to multivesicular bodies, preserves Golgi architecture, and fails to induce lipid accumulation. All together, these results identify ORF3a as a regulator of membrane organization and lipid homeostasis, showing how minimal sequence variation rewires host-cell remodelling. Graphical TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/742305v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@135032borg.highwire.dtl.DTLVardef@1633d4borg.highwire.dtl.DTLVardef@4d4115org.highwire.dtl.DTLVardef@1ebdf65_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Inflammation cellular platform (INCEPLAT) for testing anti-inflammatory compounds for SARS-CoV-2

From the early days of the COVID-19 pandemic, an excessive release of proinflammatory cytokines, such as IL6, was detected in serum from patients. As a consequence, several anti-inflammatory drugs, such as Dexamethasone (a strong corticoid), were used to counteract such cytokine storm occurring during severe disease. By contrast, pro-inflammatory interleukin 11 (IL11), a member of the IL6 family, was detected in respiratory tissues from infected patients and in experimental epithelial cellular models. In this work, human A549 lung epithelial cells were individually transduced with SARS-CoV-2 open reading frames (ORFs), resulting in a IL11 increase, which was significantly decreased after Dexamethasone treatment. The use of this cellular platform allowed us to screen for new possible anti-inflammatory compounds from Fasciola hepatica. Our results highlighted the ability of FhNEJ (Fasciola hepatica newly excysted juvenile flukes) somatic extract to decrease IL11 levels in ORF-transduced cells. These results emphasized the role of IL11 in lung epithelial inflammation, making it a potential target for future treatments of lung inflammation which occurs in COVID-19, and validate the use of these ORF-expressing cells as a cellular platform to test anti-inflammatory compounds for COVID-19 disease.

immunology↗