Related Experiment Video
Updated: Dec 27, 2025
10:12
Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
Published on: June 14, 2024
2.5K
BPIFB3 Regulates Endoplasmic Reticulum Morphology To Facilitate Flavivirus Replication
Azia S Evans1,2, Nicholas J Lennemann1,2, Carolyn B Coyne3,2,4
1Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Journal of Virology
|February 28, 2020
Summary
BPI fold-containing family B member 3 (BPIFB3) promotes dengue and Zika virus replication by inhibiting ER turnover. Depleting BPIFB3 enhances autophagy, restricts viral replication, and confirms RETREG1
Area of Science:
- Virology
- Cell Biology
- Autophagy Research
Background:
- Flaviviruses like dengue virus (DENV) and Zika virus (ZIKV) depend on endoplasmic reticulum (ER) membranes for replication.
- These viruses inhibit ER turnover by cleaving reticulophagy regulator 1 (RETREG1/FAM134B), an autophagy receptor.
- Autophagy induction is crucial for flavivirus replication, yet its interplay with viral evasion strategies is not fully understood.
Purpose of the Study:
- To investigate the role of BPI fold-containing family B member 3 (BPIFB3) in DENV and ZIKV replication.
- To elucidate the mechanism by which BPIFB3 influences ER turnover and autophagy during flavivirus infection.
- To determine the therapeutic potential of targeting BPIFB3 or RETREG1-dependent pathways.
Main Methods:
- RNA interference (RNAi) to deplete BPIFB3 and RETREG1.
- Analysis of viral replication organelle formation.
- Assessment of RETREG1-dependent reticulophagy and ER turnover.
- Viral infection assays for DENV and ZIKV.
Main Results:
- BPIFB3 acts as a positive regulator for DENV and ZIKV replication, unlike its role in enterovirus replication.
- Silencing BPIFB3 inhibits viral replication organelle formation and enhances RETREG1-dependent reticulophagy.
- Enhanced ER turnover due to BPIFB3 depletion suppresses flavivirus replication.
- The antiviral effect of BPIFB3 depletion is reversible by RETREG1 silencing.
Conclusions:
- BPIFB3 is a critical host factor essential for DENV and ZIKV replication.
- BPIFB3 regulates ER turnover, impacting flavivirus infection.
- Targeting BPIFB3 or enhancing RETREG1-dependent reticulophagy presents a potential antiviral strategy against flaviviruses.
Related Concept Videos
01:38Intralumenal Vesicles and Multivesicular Bodies
4.6K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
4.6K
01:32Export of Misfolded Proteins out of the ER
4.8K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.8K
01:31Regulation of the Unfolded Protein Response
2.9K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K
01:34Directing Proteins to the Rough Endoplasmic Reticulum
16.4K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
16.4K
02:28Leaky Scanning
5.5K
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...
5.5K
01:37The Unfolded Protein Response
6.1K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.1K