Related Experiment Video

Updated: Jan 8, 2026

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

7.7K

Viral SAM-binding proteins nsp14 and NP868R reprogram ATG4A-dependent autophagy from antiviral LC3B activity to

Yahui Li1,2, Ya Zhu1, Fei Wang1

  • 1MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, Zhejiang University, Hangzhou, China.

Autophagy
|December 23, 2025
PubMed

Insights

Viral proteins reprogram autophagy by stabilizing ATG4A mRNA, shifting activity from LC3B to GABARAP-mediated mitophagy. This immune evasion strategy enhances viral replication by suppressing innate immunity and virophagy.

Area of Science:

  • Cellular Biology
  • Virology
  • Immunology

Background:

  • The mammalian Atg8-protein family (ATG8) is crucial for selective macroautophagy/autophagy.
  • Functional distinctions of ATG8 proteins during viral infections are not well understood.

Purpose of the Study:

  • To investigate how S-adenosyl-L-methionine (SAM)-binding viral proteins influence autophagy during infection.
  • To elucidate the mechanisms by which viral proteins reprogram autophagy and evade host immunity.

Main Methods:

  • Analysis of SAM-binding viral proteins (nsp14, NP868R) and their interaction with ATG8 proteins.
  • Investigation of ATG4A mRNA stabilization and its effect on autophagic flux.
  • Assessment of innate immune responses, including interferon signaling and virophagy.
  • Evaluation of viral replication rates.

Main Results:

  • SAM-binding viral proteins stabilize ATG4A mRNA, increasing ATG4A expression.
  • Autophagic flux is redirected from LC3B-mediated virophagy to GABARAP-dependent mitophagy.
  • This shift suppresses MAVS-dependent interferon signaling and virophagy.
  • Viral replication is enhanced due to suppressed innate immune responses.

Conclusions:

  • Viral proteins employ a novel immune evasion strategy by hijacking autophagy.
  • SAM-binding viral proteins rewire autophagy from antiviral to proviral pathways.
  • Targeting ATG4A offers a potential avenue for antiviral therapies.
Keywords:
ATG4AATG8 familyGABARAPLC3Bmitophagyvirophagy

More Related Videos

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

1.4K
Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles06:58

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

1.2K

Related Concept Videos

Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
4.9K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.1K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.6K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.6K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
8.7K
Rab Cascades01:25

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
3.4K