ArticleAntimicrobial agents and chemotherapy2012
Activation of the unfolded protein response by 2-deoxy-D-glucose inhibits Kaposi's sarcoma-associated herpesvirus replication and gene expression.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Metabolic reprogramming in viral infections: the interplay of glucose metabolism and immune responses.Frontiers in immunology · 2025Review
- Physiologically Achievable Concentration of 2-Deoxy-D-Glucose Stimulates IFN-γ Secretion in Activated T Cells In Vitro.International journal of molecular sciences · 2024Article
- Rewiring of the Host Cell Metabolome and Lipidome during Lytic Gammaherpesvirus Infection Is Essential for Infectious-Virus Production.Journal of virology · 2023Article
- 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation.Virology journal · 2023Article
- Glucose and mannose analogs inhibit KSHV replication by blocking N-glycosylation and inducing the unfolded protein response.Journal of medical virology · 2023Article
- Contribution of carbohydrate-related metabolism in Herpesvirus infections.Current research in microbial sciences · 2023Article
- A network-biology led computational drug repurposing strategy to prioritize therapeutic options for COVID-19.Heliyon · 2022Article
- Molecular Mechanisms of Kaposi Sarcoma Development.Cancers · 2022Article
- Article
- Novel mutation in hexokinase 2 confers resistance to 2-deoxyglucose by altering protein dynamics.PLoS computational biology · 2022Article
- Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells.Scientific reports · 2021Article
- 2-Deoxy-d-glucose exploits increased glucose metabolism in cancer and viral-infected cells: Relevance to its use in India against SARS-CoV-2.IUBMB life · 2021Review
- Glyceraldehyde-3-Phosphate Dehydrogenase Restricted in Cytoplasmic Location by Viral GP5 Facilitates Porcine Reproductive and Respiratory Syndrome Virus Replication via Its Glycolytic Activity.Journal of virology · 2021Article
- Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections.Med (New York, N.Y.) · 2020Review
- Glycolytic inhibitor 2-deoxyglucose suppresses inflammatory response in innate immune cells and experimental staphylococcal endophthalmitis.Experimental eye research · 2020Article
- Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development.Signal transduction and targeted therapy · 2020Review
- Mitochondria in cancer.Cell stress · 2020Review
- Herpesviruses and the Unfolded Protein Response.Viruses · 2019Review
- PFKFB3 inhibition reprograms malignant pleural mesothelioma to nutrient stress-induced macropinocytosis and ER stress as independent binary adaptive responses.Cell death & disease · 2019Article
- Virus and tumor microenvironment induced ER stress and unfolded protein response: from complexity to therapeutics.Oncotarget · 2018Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Lytic replication of the Kaposi's sarcoma-associated herpesvirus (KSHV) is essential for the maintenance of both the infected state and characteristic angiogenic phenotype of Kaposi's sarcoma and thus represents a desirable therapeutic target. During the peak of herpesvirus lytic replication, viral glycoproteins are mass produced in the endoplasmic reticulum (ER). Normally, this leads to ER stress which, through an unfolded protein response (UPR), triggers phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α), resulting in inhibition of protein synthesis to maintain ER and cellular homeostasis. However, in order to replicate, herpesviruses have acquired the ability to prevent eIF2α phosphorylation. Here we show that clinically achievable nontoxic doses of the glucose analog 2-deoxy-d-glucose (2-DG) stimulate ER stress, thereby shutting down eIF2α and inhibiting KSHV and murine herpesvirus 68 replication and KSHV reactivation from latency. Viral cascade genes that are involved in reactivation, including the master transactivator (RTA) gene, glycoprotein B, K8.1, and angiogenesis-regulating genes are markedly decreased with 2-DG treatment. Overall, our data suggest that activation of UPR by 2-DG elicits an early antiviral response via eIF2α inactivation, which impairs protein synthesis required to drive viral replication and oncogenesis. Thus, induction of ER stress by 2-DG provides a new antiherpesviral strategy that may be applicable to other viruses.
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