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Host Pah1p phosphatidate phosphatase limits viral replication by regulating phospholipid synthesis
Zhenlu Zhang1,2, Guijuan He1,2, Gil-Soo Han3
1Fujian Province Key Laboratory of Plant Virology, Institute of Plant Virology, Fujian Agriculture and Forestry University, Fuzhou, Fujian, P. R. China.
Plos Pathogens
|April 13, 2018
Summary
Yeast cells lacking PAH1 show enhanced brome mosaic virus (BMV) replication and improved growth. This occurs because blocking storage lipid synthesis boosts phospholipid production, crucial for viral replication complexes and cell health during infection.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Positive-strand RNA viruses [(+)RNA viruses] replicate in membrane-bound viral replication complexes (VRCs).
- VRC formation depends on virus-induced alterations in cellular lipid synthesis.
- Pah1p, encoded by PAH1, is a phosphatidic acid phosphohydrolase involved in lipid metabolism.
Purpose of the Study:
- To investigate the role of PAH1 and its lipid metabolic pathway in brome mosaic virus (BMV) replication.
- To determine how altered lipid composition affects viral replication and host cell growth.
Main Methods:
- Utilized yeast mutants lacking PAH1 (pah1Δ) and DGK1.
- Analyzed viral replication protein localization and viral RNA levels.
- Assessed cell growth and lipid composition changes.
Main Results:
- Yeast cells lacking PAH1 (pah1Δ) exhibited a 2-fold increase in BMV genomic replication and enhanced cell growth.
- Altered lipid composition, specifically increased phospholipids, was responsible for enhanced BMV replication.
- Overexpression of a phosphatidylcholine synthesis gene (CHO2) promoted BMV replication.
Conclusions:
- Pah1p promotes storage lipid synthesis, suppressing phospholipid synthesis, which limits viral replication and cell growth.
- Manipulating lipid synthesis pathways, particularly phospholipid levels, can enhance viral replication.
- Targeting Pah1p activity could be a strategy to control viral infections and their impact on host cells.
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