Host cell glutamine metabolism as a potential antiviral target

A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in glutamine utilization and metabolism. Glutamine metabolism generates ATP and precursors for the synthesis of macromolecules to assemble progeny viruses. Some compounds derived from glutamine are used in the synthesis of purines and pyrimidines. These latter compounds are precursors for the synthesis of nucleotides. Inhibitors of glutamine transport and metabolism are potential candidate antiviral drugs. Glutamine is also an essential nutrient for the functions of leukocytes (lymphocyte, macrophage, and neutrophil), including those in virus-infected patients. The increased glutamine requirement for immune cell functions occurs concomitantly with the high glutamine utilization by host cells in virus-infected patients. The development of antiviral drugs that target glutamine metabolism must then be specifically directed at virus-infected host cells to avoid negative effects on immune functions. Therefore, the aim of this review was to describe the landscape of cellular glutamine metabolism to search for potential candidates to inhibit glutamine transport or glutamine metabolism.

The Dietary Replacement of Soybean Oil by Canola Oil Does Not Prevent Liver Fatty Acid Accumulation and Liver Inflammation in Mice.

A high-carbohydrate diet (HCD) is a well-established experimental model of accelerated liver fatty acid (FA) deposition and inflammation. In this study, we evaluated whether canola oil can prevent these physiopathological changes. We evaluated hepatic FA accumulation and inflammation in mice fed with a HCD (72.1% carbohydrates) and either canola oil (C group) or soybean oil (S group) as a lipid source for 0, 7, 14, 28, or 56 days. Liver FA compositions were analyzed by gas chromatography. The mRNA expression of acetyl-CoA carboxylase 1 (ACC1) was measured as an indicator of lipogenesis. The mRNA expression of F4/80, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-10, as mediators of liver inflammation, were also measured. The C group stored less n-6 polyunsaturated FAs (n-6 PUFAs) and had more intense lipid deposition of monounsaturated FAs (MUFAs), n-3 PUFAs, and total FAs. The C group also showed higher ACC1 expression. Moreover, on day 56, the C group showed higher expressions of the inflammatory genes F4/80, TNF-α, IL-1ß, and IL-6, as well as the anti-inflammatory IL-10. In conclusion, a diet containing canola oil as a lipid source does not prevent the fatty acid accumulation and inflammation induced by a HCD.