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Infection-induced lysine lactylation enables herpesvirus immune evasion.
Sci Adv
January 2025
Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.
Aerobic glycolysis is a hallmark of many viral infections, leading to substantial accumulation of lactate. However, the regulatory roles of lactate during viral infections remain poorly understood. Here, we report that human cytomegalovirus (HCMV) infection leverages lactate to induce widespread protein lactylation and promote viral spread.
View Article and Find Full Text PDFThe HUSH epigenetic repressor complex silences PML nuclear body-associated HSV-1 quiescent genomes.
Proc Natl Acad Sci U S A
December 2024
Université Claude Bernard Lyon 1, Centre national de la recherche scientifique (CNRS) UMR 5261, Institut national de la santé et de la recherche médicale (Inserm) U1315, Laboratoire d'Excellence (LabEx) DEV2CAN, Institut NeuroMyoGène-Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), team "Chromatin dynamics, Nuclear Domains, Virus", Lyon 69008, France.
Herpes simplex virus 1 (HSV-1) latently infected neurons display diverse patterns in the distribution of the viral genomes within the nucleus. A key pattern involves quiescent HSV-1 genomes sequestered in promyelocytic leukemia nuclear bodies (PML NBs) forming viral DNA-containing PML-NBs (vDCP NBs). Using a cellular model that replicates vDCP NB formation, we previously demonstrated that these viral genomes are chromatinized with the H3.
View Article and Find Full Text PDFLactylation of RNA mA demethylase ALKBH5 promotes innate immune response to DNA herpesviruses and mpox virus.
Proc Natl Acad Sci U S A
October 2024
Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing 210004, People's Republic of China.
Article Synopsis
- The study highlights the role of ALKBH5, an RNA demethylase, in regulating innate immunity, particularly during viral infections.
- It discovers a new posttranslational modification, lactylation, that is crucial for ALKBH5’s function in boosting antiviral responses against various herpesviruses.
- The research shows that viral infection increases lactylation of ALKBH5, which enhances the production of interferon-beta mRNA, thereby providing new insights into potential therapeutic targets for viral infections like HSV-1.
HSV-1-induced N6-methyladenosine reprogramming via ICP0-mediated suppression of METTL14 potentiates oncolytic activity in glioma.
Cell Rep
October 2024
Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Key Laboratory of Medical Molecular Virology (Ministry of Education/National Health Commission/ Chinese Academy of Medical Sciences), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pharmacy, Jinshan Hospital, Fudan University, Shanghai 201508, China. Electronic address:
Upon infection with herpes simplex virus 1 (HSV-1), the virus deploys multiple strategies to evade the host's innate immune response. However, the mechanisms governing this phenomenon remain elusive. Here, we find that HSV-1 leads to a decrease in overall m6A levels by selectively reducing METTL14 protein during early infection in glioma cells.
View Article and Find Full Text PDFRNF39 facilitates antiviral immune responses by promoting K63-linked ubiquitination of STING.
Int Immunopharmacol
December 2024
Department of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. Electronic address:
The cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS)-dependent pathway is a key DNA-sensing pathway that recognizes cytosolic DNA and plays a crucial role in initiating innate immune responses against pathogenic microbes and cancer. Various molecules have been identified as regulators of the cGAS-dependent pathway that controls innate immune responses. However, despite the important roles of Stimulator-of-interferon genes (STING) in the cGAS-dependent pathway, the regulation of its activation has not been elucidated.
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