ArticlemBio2021
Hypoxia-Inducible Factor 1α (HIF1α) Suppresses Virus Replication in Human Cytomegalovirus Infection by Limiting Kynurenine Synthesis.
Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- SARS-CoV-2 infection in hiPSC-derived neurons is cathepsin-dependent and causes differential accumulation of HIF1ɑ and phosphorylated tau.Molecular therapy. Nucleic acids · 2025Article
- Human cytomegalovirus promotesJournal of virology · 2025Article
- Human cytomegalovirus promotesbioRxiv : the preprint server for biology · 2025Article
- Oxidative Stress Enhances Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts.International journal of molecular sciences · 2025Article
- Is there a rationale for hyperbaric oxygen therapy in the patients with Post COVID syndrome? : A critical review.European archives of psychiatry and clinical neuroscience · 2024Review
- Human cytomegalovirus in breast milk is associated with milk composition and the infant gut microbiome and growth.Nature communications · 2024Article
- Role of aryl hydrocarbon receptors in infection and inflammation.Frontiers in immunology · 2024Review
- Human Cytomegalovirus in breast milk is associated with milk composition, the infant gut microbiome, and infant growth.bioRxiv : the preprint server for biology · 2023Article
- When AHR signaling pathways meet viral infections.Cell communication and signaling : CCS · 2023Review
- TNFα-induced metabolic reprogramming drives an intrinsic anti-viral state.PLoS pathogens · 2022Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cytomegalovirus (HCMV) replication depends on the activities of several host regulators of metabolism. Hypoxia-inducible factor 1α (HIF1α) was previously proposed to support virus replication through its metabolic regulatory function. HIF1α protein levels rise in response to HCMV infection in nonhypoxic conditions, but its effect on HCMV replication was not investigated. We addressed the role of HIF1α in HCMV replication by generating primary human cells with HIF1α knocked out using CRISPR/Cas9. When HIF1α was absent, we found that HCMV replication was enhanced, showing that HIF1α suppresses viral replication. We used untargeted metabolomics to determine if HIF1α regulates metabolite concentrations in HCMV-infected cells. We discovered that in HCMV-infected cells, HIF1α suppresses intracellular and extracellular concentrations of kynurenine. HIF1α also suppressed the expression of indoleamine 2,3-dioxygenase 1 (IDO1), the rate-limiting enzyme in kynurenine synthesis. In addition to its role in tryptophan metabolism, kynurenine acts as a signaling messenger by activating aryl hydrocarbon receptor (AhR). Inhibiting AhR reduces HCMV replication, while activating AhR with an exogenous ligand increases virus replication. Moreover, we found that feeding kynurenine to cells promotes HCMV replication. Overall, our findings indicate that HIF1α reduces HCMV replication by regulating metabolism and metabolite signaling.
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