bims-mevinf 2023-08-27 papers

Viruses. 2023 Aug 10. pii: 1716. [Epub ahead of print]15(8):

Components of the Nucleotide Salvage Pathway Increase Frog Virus 3 (FV3) Replication.

Samantha R Logan, Mark Seegobin, R J Neil Emery, Craig R Brunetti.

Viruses are obligate intracellular parasites that alter host metabolic machinery to obtain energy and macromolecules that are pivotal for replication. Ranavirus, including the type species of the genus frog virus 3 (FV3), represent an ecologically important group of viruses that infect fish, amphibians, and reptiles. It was established that fatty acid synthesis, glucose, and glutamine metabolism exert roles during iridovirus infections; however, no information exists regarding the role of purine metabolism. In this study, we assessed the impact of exogenously applied purines adenine, adenosine, adenosine 5'-monophosphate (AMP), inosine 5'-monophosphate (IMP), inosine, S-adenosyl-L-homocysteine (SAH), and S-adenosyl-L-methionine (SAM) on FV3 replication. We found that all compounds except for SAH increased FV3 replication in a dose-dependent manner. Of the purines investigated, adenine and adenosine produced the most robust response, increasing FV3 replication by 58% and 51%, respectively. While all compounds except SAH increased FV3 replication, only adenine increased plaque area. This suggests that the stimulatory effect of adenine on FV3 replication is mediated by a mechanism that is at least in part independent from the other compounds investigated. Our results are the first to report a response to exogenously applied purines and may provide insight into the importance of purine metabolism during iridoviral infection.

Keywords: FV3; Iridoviridae; adenine; adenosine; frog virus 3; nucleotide metabolism; purine salvage; ranavirus; viral replication

DOI: https://doi.org/10.3390/v15081716

Pharmaceuticals (Basel). 2023 Aug 04. pii: 1104. [Epub ahead of print]16(8):

Early Events after Herpes Simplex Virus-Type 1 Entry Are Necessary for the Release of Gamma-Hydroxybutyrate upon Acute Infection.

Faith O Osinaga, Yu-Chih Chen, Madan K Kharel, Yan Waguespack, Sichu Li, Shaochung Victor Hsia.

We reported that gamma-hydroxybutyrate (GHB) is released upon Herpes Simplex Virus Type-1 (HSV-1) acute infection. However, the cellular biochemical processes involved in the production of GHB in infected cells are unclear. This study aims to shed light on the biochemical pathway and the stage within the viral life cycle responsible for the release of GHB in infected cells. UV-inactivation, acyclovir (ACV), and cycloheximide (CHX) treatments were used to inhibit HSV-1 replication at various stages. Vero cells treated with UV-inactivated HSV-1 significantly decreased GHB production. However, ACV or CHX treatments did not affect GHB production. We also showed that inhibition of glycolytic enzyme enolase by sodium fluoride (NaF) significantly reduces GHB production upon infection. This finding suggests that suppression of glycolytic activity negatively affects cellular GHB production. Our data also indicated that succinic semialdehyde dehydrogenase, an enzyme involved in the shunt of the tricarboxylic acid (TCA) cycle to generate succinic acid, was decreased upon infection, suggesting that infection may trigger the accumulation of succinic semialdehyde, causing the production of GHB. Although the precise mechanism has yet to be defined, our results suggest that early events following infection modulates the release of GHB, which is generated through the metabolic pathways of glycolysis and TCA cycle.

Keywords: UPLC-MRM-MS; gamma-hydroxybutyrate; mass spectrometry; virology

DOI: https://doi.org/10.3390/ph16081104

Metabolites. 2023 Aug 15. pii: 948. [Epub ahead of print]13(8):

Metabolomics Approaches for the Diagnosis, Treatment, and Better Disease Management of Viral Infections.

Haya Al-Sulaiti, Jehad Almaliti, C Benjamin Naman, Asmaa A Al Thani, Hadi M Yassine.

Metabolomics is an analytical approach that involves profiling and comparing the metabolites present in biological samples. This scoping review article offers an overview of current metabolomics approaches and their utilization in evaluating metabolic changes in biological fluids that occur in response to viral infections. Here, we provide an overview of metabolomics methods including high-throughput analytical chemistry and multivariate data analysis to identify the specific metabolites associated with viral infections. This review also focuses on data interpretation and applications designed to improve our understanding of the pathogenesis of these viral diseases.

Keywords: COVID-19; HBV; HCMV; HCV; HIV; LC-MS; NMR; influenza; metabolomics; viral infections

DOI: https://doi.org/10.3390/metabo13080948

Biosci Rep. 2023 Aug 22. pii: BSR20230372. [Epub ahead of print]

Sensing nucleotide composition in virus RNA.

Raymon Lo, Daniel Gonçalves-Carneiro.

Nucleotide composition plays a crucial role in the structure, function and recognition of RNA molecules. During infection, virus RNA is exposed to multiple endogenous proteins that detect local or global compositional biases and interfere with virus replication. Recent advancements in RNA:protein mapping technologies have enabled the identification of general RNA-binding preferences in the human proteome at basal level and in the context of virus infection. In this review, we explore how cellular proteins recognise nucleotide composition in virus RNA and the impact these interactions have on virus replication. Proteins binding G-rich and C-rich sequences are common examples of how host factors detect and limit infection, and, in contrast, viruses may have evolved to purge their genomes from such motifs. We also give examples of how human RNA-binding proteins inhibit virus replication, not only by destabilising virus RNA, but also by interfering with viral protein translation and genome encapsidation. Understanding the interplay between cellular proteins and virus RNA composition can provide insights into host-virus interactions and uncover potential targets for antiviral strategies.

Keywords: Coding Bias; Nucleotide; Virus; antiviral; host-virus interaction

DOI: https://doi.org/10.1042/BSR20230372