Argininosuccinate synthetase 1 depletion produces a metabolic state conducive to herpes simplex virus 1 infection

作者：Grady Sarah L; Purdy John G; Rabinowitz Joshua D; Shenk Thomas^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(51): E5006-E5015.

DOI：10.1073/pnas.1321305110

• metabolomics
• herpesviruses

Herpes simplex virus 1 (HSV-1) infection triggers specific metabolic changes in its host cell. To explore the interactions between cellular metabolism and HSV-1 infection, we performed an siRNA screen of cellular metabolic genes, measuring their effect on viral replication. The screen identified multiple enzymes predicted to influence HSV-1 replication, including argininosuccinate synthetase 1 (AS1), which consumes aspartate as part of de novo arginine synthesis. Knockdown of AS1 robustly enhanced viral genome replication and the production of infectious virus. Using high-resolution liquid chromatography-mass spectrometry, we found that the metabolic phenotype induced by knockdown of AS1 in human fibroblasts mimicked multiple aspects of the metabolic program observed during HSV-1 infection, including an increase in multiple nucleotides and their precursors. Together with the observation that AS1 protein and mRNA levels decrease during wild-type infection, this work suggests that reduced AS1 activity is partially responsible for the metabolic program induced by infection.

• 出版日期2013-12-17