Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding

Monica L Husby1,2, Souad Amiar1,2, Laura I Prugar3

  • 1Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.

EMBO Reports
|September 12, 2022
PubMed

Insights

The Ebola virus matrix protein VP40 clusters phosphatidylserine (PS) to promote viral budding. The drug fendiline inhibits this PS clustering, reducing viral spread and entry.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Phosphatidylserine (PS) is essential for the assembly and spread of enveloped viruses.
  • The Ebola virus matrix protein VP40 plays a key role in viral budding.

Purpose of the Study:

  • To investigate how Ebola virus VP40 induces phosphatidylserine clustering.
  • To explore the mechanism of fendiline's inhibition of Ebola virus replication.

Main Methods:

  • In vitro assays including imaging, viral budding, and viral entry assays.
  • Measurement of PS content in mammalian cells and plasma membranes.

Main Results:

  • Ebola virus VP40 induces phosphatidylserine clustering, promoting viral budding.
  • Fendiline reduces PS clustering and viral budding and entry.
  • Fendiline treatment lowers cellular PS and impairs VP40's ability to form new virus particles.
  • Particles from fendiline-treated cells exhibit altered morphology and reduced infectivity.

Conclusions:

  • Ebola virus matrix protein VP40 utilizes phosphatidylserine clustering for efficient viral assembly, budding, and spread.
  • Fendiline represents a potential therapeutic strategy by targeting PS clustering to inhibit Ebola virus replication.

Related Concept Videos

Vesicular Tubular Clusters01:45

Vesicular Tubular Clusters

After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
2.6K
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

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...
3.7K
Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.2K
Synthesis of Phosphatidylcholine in the ER Membrane01:27

Synthesis of Phosphatidylcholine in the ER Membrane

The ER synthesizes lipids for building cell membranes and performing cellular functions such as energy storage and signaling. The lipid synthesis machinery embedded in the ER membrane primarily collects all reactants from the cytosol. Following synthesis, the secretory pathway and the ER contact sites distribute these lipids to other cellular organelles. Additionally, the energy-rich triacylglycerides are transported from the ER via lipid droplets.
The major components of all eukaryotic cell...
3.2K
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...
5.2K