bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.10.21.619359

Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells

Bonglack, E. N.·Hill, K. K.·Barry, A. P.·Bartlett, A.·Castellano-Escuder, P.·Hirschey, M. D.·Luftig, M. A.
View original source ↗Export metadata ↓

Abstract

Epstein-Barr virus (EBV) is a gamma herpesvirus that infects up to 95% of the human population by adulthood, typically remaining latent in the host memory B cell pool. In immunocompromised individuals, EBV can drive the transformation and rapid proliferation of infected B cells, ultimately resulting in neoplasia. The same transformation process can be induced in vitro, with EBV-infected peripheral blood mononuclear cells (PBMCs) forming immortalized lymphoblastoid cell lines (LCLs) within weeks. In this study, we found that the fatty acid desaturases stearoyl-CoA desaturase 1 (SCD1) and fatty acid desaturase 2 (FADS2) are upregulated by EBV, and crucial for EBV-induced B cell proliferation. Additionally, we found that pharmacological and genetic inhibition of both SCD1 and FADS2 results in a significantly greater reduction in proliferation and cell cycle arrest, compared to perturbing either enzyme individually. Additionally, we found that inhibiting either SCD1 or FADS2 alone hypersensitizes LCLs to palmitate-induced apoptosis, recapitulating studies in other tissue types. Further lipidomic and metabolic analysis of dual SCD1/FADS2-inhibited LCLs revealed an increase in free unsaturated fatty acids, a reduction of oxidative phosphorylation, and a reduction of glycolysis, thereby linking the activity of SCD1 and FADS2 to overall growth-promoting metabolism. Lastly, we show that SCD1 and FADS2 are important in the growth of clinically derived EBV+ immunoblastic lymphoma cells. Collectively, these data demonstrate a previously uncharacterized role of lipid desaturation in EBV+ transformed B cell proliferation, revealing a metabolic pathway that can be targeted in future anti-lymphoma therapies.

Source connections

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bonglack, E. N., Hill, K. K., Barry, A. P., Bartlett, A., Castellano-Escuder, P., Hirschey, M. D., Luftig, M. A.. 2024-10-21. Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells. https://doi.org/10.1101/2024.10.21.619359

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Reverse Transcription Loop-Mediated Isothermal Amplification Combined with Lateral Flow Assay (RT-LAMP-LFA) for Rapid Detection of the 2026 Bundibugyo Virus (BDBV) Outbreak Strain

Making accurate diagnosis is a critical first step in patient management and control for emerging and re-emerging disease outbreaks. Bundibugyo virus (BDBV) is a filovirus that causes Ebola disease, and the 2026 outbreak highlights the need for rapid diagnostic approaches that can be deployed in settings with limited laboratory infrastructure. Here, we developed a reverse transcription loop-mediated isothermal amplification-lateral flow assay (RT-LAMP-LFA) for rapid detection of the 2026 BDBV outbreak strain. LAMP primers were designed based on the genome sequence of the 2026 outbreak strain, and the conservation of the primer binding sites among all available 2026 outbreak genomes was confirmed in silico. LAMP primers were evaluated for analytical specificity and sensitivity using in vitro-transcribed RNA (ivtRNA) from BDBV and other filoviruses, as well as RNA derived from arboviruses and mammalian cells. Amplification products were detected using a Chromatography-Printed Array Strip (C-PAS) lateral flow platform. The newly designed primers specifically detected the presence of BDBV RNA without nonspecific amplification of the other viral or cellular RNA samples tested. Consistent amplification was observed down to 103 copies per reaction. In addition, BDBV viral RNA was successfully amplified, and the amplification products were detected using C-PAS, with the total workflow being completed within 25 min. These findings demonstrate the analytical specificity and sensitivity of the developed RT-LAMP-LFA assay and its compatibility with rapid visual lateral flow detection, supporting its potential application as a point-of-care approach for BDBV detection.

microbiology↗
bioRxiv2026

Divergent methane production and microbial community responses to carbon enrichment in freshwater wetland sediments

Methane (CH4) accumulation in wetland sediments reflects interactions among organic matter, sediment chemistry, and microbial communities. We combined depth-resolved field characterization across four wetland habitats in northern Israel with complementary incubations to examine methane accumulation and responses to labile-carbon enrichment. Sediment cores were characterized using Rock-Eval analysis, porewater chemistry, oxygen profiling at three sites, and mcrA amplicon sequencing. High CH4 concentrations occurred under contrasting conditions: Ein Nimfit (EN) contained approximately 12% total organic carbon and reached 2.1 mM CH4, whereas Ein Afek site EA2 contained approximately 5% carbon and accumulated 0.7-1.7 mM CH4. Both showed sulfate depletion, but EN exhibited pronounced sulfide accumulation, whereas EA2 showed greater dissolved iron and nutrient enrichment. Their classified methanogenic assemblages also differed. EA1 remained methane poor despite increasing carbon content with depth, while EA3 combined low carbon content and CH4 accumulation with detectable methanogens and lower methanogenic diversity. In a 36-day bottle experiments using sediments from two of the four wetland habitats, sucrose-amended EA3 exhibited a transient maximum of 18.8 mmol collected CH4 kg-1 wet sediment during Days 22-29, whereas EN reached its highest collected amount during Days 29-36. Methane proportions increased before the large output increase in EA3 but remained comparatively stable and high in EN. Soluble chemical oxygen demand trajectories and microbial community changes also differed. These findings identify distinct biogeochemical settings supporting methane accumulation and demonstrate methanogenic potential in low-CH4 sediment, emphasizing the complementary information provided by field profiles, microbial characterization, and exploratory enrichment experiments.

microbiology↗
bioRxiv2026

The absence of microbiome in germ-free mice exacerbates the pathogenicity of mouse-adapted SARS-CoV-2 MA10

Germ-free mice, which are devoid of microbiota, provide a powerful system to define the contribution of the microbiome to host responses during infection. Severe COVID-19 outcomes are associated with multiple comorbidities that are themselves characterized by microbiome dysbiosis; however, the causal role of the microbiota in SARS-CoV-2 pathogenesis remains poorly understood. Here, we use germ-free mouse models to evaluate the impact of the microbiome on disease severity following infection with mouse-adapted SARS-CoV-2 MA10. Comparison with conventionally housed mice revealed that the absence of the microbiome markedly exacerbates SARS-CoV-2-induced disease in both C57BL/6 and Swiss Webster backgrounds. Germ-free mice exhibited greater weight loss, impaired lung function, worsened pulmonary pathology, and pronounced alterations in circulating cytokine and chemokine profiles compared with conventional controls. These findings show that resident microbiota limit SARS-CoV-2 pathogenicity and establish germ-free COVID-19 models as a powerful platform to identify protective microbial taxa and microbiota-based interventions to reduce severe disease.

microbiology↗