ArticleProceedings of the National Academy of Sciences of the United States of America2017
ACSS2-mediated acetyl-CoA synthesis from acetate is necessary for human cytomegalovirus infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 84 citations in OpenAlex.
- An acetylation-dependent switch underlies host disease tolerance during streptococcal infection.Scientific reports · 2026Article
- ATP-citrate lyase is a critical regulator of physiological and pathological angiogenesis.Angiogenesis · 2026Article
- Cancer Stem Cells Shift Metabolite Acetyl-Coenzyme A to Abrogate the Differentiation of CD103Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- IntegratingFrontiers in immunology · 2026Review
- Catabolic rewiring in cancer impacts dietary interventions.Communications biology · 2025Review
- ACSS2 involved in acetyl-CoA synthesis regulates skeletal muscle function.FEBS letters · 2025Article
- Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications.Molecular biomedicine · 2025Review
- Article
- The Nuclear Localization of ACLY Guards Early Embryo Development Through Recruiting P300 and HAT1 to Promote Histone Acetylation and Transcription.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrative transcriptomic and proteomic analyses reveal that carbon metabolism and complement system of Madin Darby Bovine Kidney cells are affected by bovine coronavirus infection.BMC veterinary research · 2025Article
- KRAS G12V mutation-selective requirement for ACSS2 in colorectal adenoma formation.Cell reports · 2025Article
- The metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling.Frontiers in immunology · 2025Review
- Acetate Metabolism in Urological Health and Disease.Serican journal of medicine · 2024Article
- Role of ATP citrate lyase and its complementary partner on fatty acid synthesis in gastric cancer.Scientific reports · 2024Article
- Stimulation of neutral lipid synthesis via viral growth factor signaling and ATP citrate lyase during vaccinia virus infection.Journal of virology · 2024Article
- Hypoxia-inducible factor-1α-deficient adipose-tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein-1.Laboratory animal research · 2024Article
- Activation of acetyl-CoA synthetase 2 mediates kidney injury in diabetic nephropathy.JCI insight · 2023Article
- Acetate controls endothelial-to-mesenchymal transition.Cell metabolism · 2023Article
- NFYA promotes malignant behavior of triple-negative breast cancer in mice through the regulation of lipid metabolism.Communications biology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Recent studies have shown that human cytomegalovirus (HCMV) can induce a robust increase in lipid synthesis which is critical for the success of infection. In mammalian cells the central precursor for lipid biosynthesis, cytosolic acetyl CoA (Ac-CoA), is produced by ATP-citrate lyase (ACLY) from mitochondria-derived citrate or by acetyl-CoA synthetase short-chain family member 2 (ACSS2) from acetate. It has been reported that ACLY is the primary enzyme involved in making cytosolic Ac-CoA in cells with abundant nutrients. However, using CRISPR/Cas9 technology, we have shown that ACLY is not essential for HCMV growth and virally induced lipogenesis. Instead, we found that in HCMV-infected cells glucose carbon can be used for lipid synthesis by both ACLY and ACSS2 reactions. Further, the ACSS2 reaction can compensate for the loss of ACLY. However, in ACSS2-KO human fibroblasts both HCMV-induced lipogenesis from glucose and viral growth were sharply reduced. This reduction suggests that glucose-derived acetate is being used to synthesize cytosolic Ac-CoA by ACSS2. Previous studies have not established a mechanism for the production of acetate directly from glucose metabolism. Here we show that HCMV-infected cells produce more glucose-derived pyruvate, which can be converted to acetate through a nonenzymatic mechanism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.