4.6 Article

African Swine Fever Virus Regulates Host Energy and Amino Acid Metabolism To Promote Viral Replication

期刊

JOURNAL OF VIROLOGY
卷 96, 期 4, 页码 -

出版社

AMER SOC MICROBIOLOGY

关键词

ASFV; metabolomics; TCA cycle; lactate; RIG-I

类别

资金

  1. National Key R&D Program of China [2021YFD1800100]
  2. National Natural Science Foundation of China [31941002, 32170161]
  3. Technology Major Project of Gansu Province [20ZD7A006, NCC0006]
  4. Chinese Academy of Agricultural Science and Technology Innovation Project [CAAS-ZDRW202006, CAAS-ASTIP-2021-LVRI]
  5. Lanzhou Veterinary Research Institute [CAAS-ASTIP-JBGS-20210101]

向作者/读者索取更多资源

This study analyzed the impact of African swine fever virus (ASFV) infection on the cellular metabolism of the host. It found that ASFV infection increased host TCA cycle and amino acid metabolism, and identified mechanisms by which ASFV inhibits host innate immune responses. These findings are important for guiding the design of prevention strategies against ASFV.
African swine fever is one of the most serious viral diseases caused by African swine fever virus (ASFV). The metabolic changes induced by ASFV infection remain unknown. Here, porcine alveolar macrophages (PAMs) infected with ASFV was analyzed by ultrahigh-performance liquid chromatography-quadrupole time-of flight tandem mass spectrometry (UHPLC-QTOF-MS) in combination with multivariate statistical analysis. A total of 90 metabolites were significantly changed after ASFV infection, and most of them were amino acids and tricarboxylic acid (TCA) cycle intermediates. ASFV infection induced an increase in most of amino acids in the host during the early stages of infection, and amino acids decreased in the late stages of infection. ASFV infection did not significantly affect the glycolysis pathway, whereas it induced increases in citrate, succinate, alpha-ketoglutarate, and oxaloacetate levels in the TCA cycle, suggesting that ASFV infection promoted the TCA cycle. The activities of aspartate aminotransferase and glutamate production were significantly elevated in ASFV-infected cells and pigs, resulting in reversible transition between TCA cycle and amino acid synthesis. Aspartate, glutamate, and TCA cycle were essential for ASFV replication. In addition, ASFV infection induced an increase in lactate level using lactate dehydrogenase, which led to low expression of beta interferon (IFN-beta) and increased ASFV replication. Our data, for the first time, indicate that ASFV infection controls IFN-beta production through RIG-I-mediated signaling pathways. These data identified a novel mechanism evolved by ASFV to inhibit host innate immune responses and provide insights for development of new preventive or therapeutic strategies targeting the altered metabolic pathways. IMPORTANCE In order to promote viral replication, viruses often cause severe immunosuppression and seize organelles to synthesize a large number of metabolites required for self-replication. African swine fever virus (ASFV) has developed many strategies to evade host innate immune responses. However, the impact of ASFV infection on host cellular metabolism remains unknown. Here, for the first time, we analyzed the metabolomic profiles of ASFV-infected PAMs. ASFV infection increased host TCA cycle and amino acid metabolism. Aspartate, glutamate, and TCA cycle promoted ASFV replication. ASFV infection also induced the increase of lactate production to inhibit innate immune responses for self-replication. This study identified novel immune evasion mechanisms utilized by ASFV and provided insights into ASFV-host interactions, which is critical for guiding the design of new prevention strategies against ASFV targeting the altered metabolic pathways.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据