The autophagy machinery interacts with EBV capsids during viral envelope release.
Maria Pena-FranceschLiliana Danusia VanoaicaGao-Feng ZhuMichael StumpeDevanarayanan Siva SankarHeike NowagAlma Delia Valencia-CamargoWolfgang HammerschmidtJoern DengjelLaure-Anne LigeonChristian MünzPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
Autophagy serves as a defense mechanism against intracellular pathogens, but several microorganisms exploit it for their own benefit. Accordingly, certain herpesviruses include autophagic membranes into their infectious virus particles. In this study, we analyzed the composition of purified virions of the Epstein-Barr virus (EBV), a common oncogenic γ-herpesvirus. In these, we found several components of the autophagy machinery, including membrane-associated LC3B-II, and numerous viral proteins, such as the capsid assembly proteins BVRF2 and BdRF1. Additionally, we showed that BVRF2 and BdRF1 interact with LC3B-II via their common protein domain. Using an EBV mutant, we identified BVRF2 as essential to assemble mature capsids and produce infectious EBV. However, BdRF1 was sufficient for the release of noninfectious viral envelopes as long as autophagy was not compromised. These data suggest that BVRF2 and BdRF1 are not only important for capsid assembly but together with the LC3B conjugation complex of ATG5-ATG12-ATG15L1 are also critical for EBV envelope release.
Keyphrases
- epstein barr virus
- cell death
- diffuse large b cell lymphoma
- endoplasmic reticulum stress
- signaling pathway
- sars cov
- oxidative stress
- simultaneous determination
- mass spectrometry
- liquid chromatography
- binding protein
- electronic health record
- high resolution
- machine learning
- big data
- antimicrobial resistance
- wild type