WSSV-induced reversal of the malate-aspartate shuttle facilitates viral replication in shrimp hemocytes Article Swipe
Fang-Jyun Guo
,
Kuan-Lun Huang
,
Cong-Yan Chen
,
Shu Wen Cheng
,
Yen Siong Ng
,
Han-Ching Wang
,
Fang-Jyun Guo
,
Kuan-Lun Huang
,
Cong-Yan Chen
,
Shu Wen Cheng
,
Yen Siong Ng
,
Han-Ching Wang
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1186/s12964-025-02506-3
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1186/s12964-025-02506-3
Background White spot syndrome virus (WSSV), one of the most devastating pathogens in global shrimp aquaculture, has been shown to hijack and reprogram host metabolic pathways to support its replication. Among the various host metabolic circuits, the malate-aspartate shuttle (MAS) is a key redox-balancing mechanism that facilitates the translocation of cytosolic NADH into mitochondria, thereby sustaining glycolysis and mitochondrial function. To date, however, the involvement of MAS in WSSV pathogenesis has not been documented. Methods In this study, we investigated the role of the MAS pathway in WSSV replication. We first assessed the mRNA level changes of MAS-related genes in WSSV infected shrimp. dsRNA-mediated gene silencing was also employed to examine its impact on the virus replication. To determine the direction of MAS during WSSV infection, we first silenced the MAS-related genes (e.g., GOT1 or GOT2), and subsequently replenished the corresponding metabolite to assess whether it could rescue the virus replication. Results At the viral genome replication stage of WSSV infection (12 hpi), significant upregulation of key MAS-related genes, including Lv GOT1, Lv GOT2, Lv MDH1, Lv AGC, and Lv OGC, was observed in hemocytes of infected shrimp. Functional knockdown of these genes by in vivo dsRNA-mediated gene silencing significantly reduced WSSV gene expression and viral genome copy number, indicating that MAS activity is required for efficient WSSV replication. Furthermore, metabolite rescue experiments revealed a potential reversal of the MAS flux during the infection: supplementation with aspartate or α-ketoglutarate restored viral replication in Lv GOT1-silenced shrimp, while oxaloacetate supplementation reversed the lowered replication caused by Lv MDH1 silencing. Conclusion This study demonstrates that WSSV activates the host MAS pathway to facilitate its replication and highlights the dynamic reprogramming of redox-associated mitochondrial metabolism in response to WSSV infection. The WSSV-induced reversed MAS might supply specific metabolites such as aspartate needed for virus replication or to prevent the TCA shut down.
Related Topics
Concepts
Biology
Gene silencing
Viral replication
Gene knockdown
White spot syndrome
Gene
Virus
Virology
Cell biology
Shrimp
Glycolysis
RNA interference
Downregulation and upregulation
Viral pathogenesis
Metabolic pathway
Genome
Viral life cycle
Genetics
RNA silencing
Pentose phosphate pathway
Gene expression
Metabolite
Anaerobic glycolysis
Cytosol
microRNA
Mitochondrion
Microbiology
Gene expression profiling
Regulation of gene expression
Hexokinase
Pathogenesis
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s12964-025-02506-3
- https://link.springer.com/content/pdf/10.1186/s12964-025-02506-3.pdf
- OA Status
- gold
- References
- 58
- OpenAlex ID
- https://openalex.org/W7106665581
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W7106665581Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1186/s12964-025-02506-3Digital Object Identifier
- Title
-
WSSV-induced reversal of the malate-aspartate shuttle facilitates viral replication in shrimp hemocytesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-11-26Full publication date if available
- Authors
-
Fang-Jyun Guo, Kuan-Lun Huang, Cong-Yan Chen, Shu Wen Cheng, Yen Siong Ng, Han-Ching Wang, Fang-Jyun Guo, Kuan-Lun Huang, Cong-Yan Chen, Shu Wen Cheng, Yen Siong Ng, Han-Ching WangList of authors in order
- Landing page
-
https://doi.org/10.1186/s12964-025-02506-3Publisher landing page
- PDF URL
-
https://link.springer.com/content/pdf/10.1186/s12964-025-02506-3.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://link.springer.com/content/pdf/10.1186/s12964-025-02506-3.pdfDirect OA link when available
- Concepts
-
Biology, Gene silencing, Viral replication, Gene knockdown, White spot syndrome, Gene, Virus, Virology, Cell biology, Shrimp, Glycolysis, RNA interference, Downregulation and upregulation, Viral pathogenesis, Metabolic pathway, Genome, Viral life cycle, Genetics, RNA silencing, Pentose phosphate pathway, Gene expression, Metabolite, Anaerobic glycolysis, Cytosol, microRNA, Mitochondrion, Microbiology, Gene expression profiling, Regulation of gene expression, Hexokinase, PathogenesisTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
-
58Number of works referenced by this work
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