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Updated: Dec 21, 2025

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
Published on: March 14, 2021
The hypothetical role of phosphatidic acid in subverting ER membranes during SARS-CoV infection
1Centre de Recherche en Biologie cellulaire de Montpellier (CRBM), University of Montpellier - CNRS, Montpellier, France.
Abstract:
Positive sense (+) RNA viruses exploit membranes from a variety of cellular organelles to support the amplification of their genomes. This association concurs with the formation of vesicles whose main morphological feature is that of being wrapped by a double membrane. In the case of the SARS-CoV virus, the outer membrane is not discrete for each vesicle, but seems to be continuous and shared between many individual vesicles, a difference with other +RNA viruses whose nature has remained elusive. I present morphological, biochemical and pharmacological arguments defending the striking analogy of this arrangement and that of entangled, nascent Lipid Droplets whose birth has been aborted by an excess of Phosphatidic Acid. Since Phosphatidic Acid can be targeted with therapeutical purposes, considering this working hypothesis may prove important in tackling SARS-CoV infection.
Insights
SARS-CoV uses unique double-membraned vesicles for genome replication. This structure resembles aborted lipid droplets, suggesting Phosphatidic Acid as a therapeutic target for SARS-CoV infection.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Positive-sense RNA viruses utilize cellular membranes for genome replication.
- Vesicle formation is a common feature, typically with double membranes.
- SARS-CoV exhibits a unique continuous outer membrane shared among vesicles, unlike other +RNA viruses.
Purpose of the Study:
- To investigate the unique membrane structures associated with SARS-CoV replication.
- To propose a novel hypothesis regarding the origin of these structures.
- To identify potential therapeutic targets for SARS-CoV infection.
Main Methods:
- Morphological analysis of viral replication complexes.
- Biochemical characterization of vesicle-associated components.
- Pharmacological studies targeting specific cellular pathways.
Main Results:
- SARS-CoV replication vesicles share a continuous outer membrane, differing from other +RNA viruses.
- This arrangement shows a striking morphological analogy to nascent lipid droplets.
- Aborted lipid droplet formation, potentially due to excess Phosphatidic Acid, is proposed.
Conclusions:
- The unique membrane structure in SARS-CoV infection may originate from aberrant lipid droplet biogenesis.
- Phosphatidic Acid is identified as a potential therapeutic target.
- This hypothesis offers a new avenue for developing anti-SARS-CoV strategies.
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