Related Experiment Video
Updated: May 2, 2026
06:03
Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
7.0K
UVRAG is required for virus entry through combinatorial interaction with the class C-Vps complex and SNAREs
Sara Dolatshahi Pirooz1, Shanshan He, Tian Zhang
1Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033.
Summary
UV-radiation resistance-associated gene (UVRAG) is crucial for enveloped virus entry into host cells. It facilitates viral transport and fusion by interacting with protein complexes, offering a potential target for antiviral therapies.
Area of Science:
- Virology
- Cell Biology
- Molecular Mechanisms of Viral Entry
Background:
- Enveloped viruses utilize the host endomembrane system for cell entry, involving vesicle transport, endosomal fusion, and SNARE-mediated processes.
- The precise molecular machinery governing viral fusion within endosomes remains incompletely understood.
- Autophagy-related proteins are increasingly recognized for roles beyond their canonical functions.
Purpose of the Study:
- To elucidate the role of UV-radiation resistance-associated gene (UVRAG) in the entry mechanism of enveloped viruses.
- To identify the specific protein interactions and pathways regulated by UVRAG during viral entry.
- To explore the potential of targeting UVRAG for antiviral therapeutic strategies.
Main Methods:
- Investigated the requirement of UVRAG for the entry of negative-strand RNA viruses like influenza A and vesicular stomatitis virus.
- Utilized biochemical assays to examine the interactions between UVRAG, the class C vacuolar protein sorting (C-Vps) complex, and endosomal SNARE proteins (STX7, STX8, Vti1b).
- Assessed the role of vesicle-associated membrane protein 8 (VAMP8) in viral entry by inhibiting its function and observing the effects on viral infectivity.
Main Results:
- UVRAG is essential for the entry of influenza A and vesicular stomatitis viruses, independent of interferon and autophagy pathways.
- UVRAG mediates viral endocytic transport and membrane penetration by interacting with the C-Vps complex and specific endosomal SNAREs.
- UVRAG promotes the assembly of a fusogenic SNARE complex by stimulating VAMP8 translocation to virus-bearing endosomes, a process critical for viral fusion.
- Inhibition of VAMP8, but not VAMP7, significantly impaired viral entry, confirming VAMP8's specific role in this UVRAG-dependent pathway.
Conclusions:
- UVRAG plays a critical role in regulating enveloped virus entry by orchestrating the assembly of a specific fusogenic SNARE complex.
- The UVRAG-C-Vps-SNARE pathway represents a novel mechanism governing viral fusion and entry into host cells.
- Targeting the UVRAG-mediated viral entry pathway presents a promising avenue for the development of new antiviral therapeutics.
Related Concept Videos
01:43SNAREs and Membrane Fusion
10.4K
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
10.4K
01:10Retrovirus Life Cycles
43.0K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
43.0K
00:56Viral Structure
59.0K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
59.0K
00:50What are Viruses?
109.5K
Overview
109.5K
01:14Rab Proteins
4.0K
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...
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...
4.0K
00:57Viral Recombination
22.3K
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
22.3K