bims-mevinf 2024-12-22 papers

Virol J. 2024 Dec 19. 21(1): 324

The importance of paying attention to the role of lipid-lowering drugs in controlling dengue virus infection.

Omer Qutaiba B Allela, Mohamad Ghazanfari Hashemi, Seyede Mozhgan Heidari, Radhwan Abdul Kareem, Hayder Naji Sameer, Mohaned Adil, Shaylan Kalavi.

The Flaviviridae family includes the dengue virus (DENV). About half of the world's population is in danger because of the estimated 390 million infections and 96 million symptomatic cases that occur each year. An effective treatment for dengue fever (DF) does not yet exist. Therefore, a better knowledge of how viral proteins and virus-targeted medicines may exert distinct functions depending on the exact cellular region addressed may aid in creating much-needed antiviral medications. Lipids facilitate the coordination of many viral replication phases, from entrance to dissemination. In addition, flaviviruses masterfully plan a significant rearrangement of the host cell's lipid metabolism to foster the growth of new viruses. Recent research has consistently shown the significance of certain lipid classes in flavivirus infections. For instance, in DENV-infected cells, overall cellular cholesterol (CHO) levels are only a little altered, and DENV replication is significantly reduced when CHO metabolism is inhibited. Moreover, statins significantly decrease DENV serotype 2 (DENV-2) titers, indicating that CHO is a prerequisite for the dengue viral cycle. Furthermore, many Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are now being evaluated in human research. A new pharmacological target for the management of high CHO is PCSK9. Moreover, suppression of PCSK9 has been proposed as a possible defense against DENV. Numerous studies have generally recommended the use of lipid-lowering medications to suppress the DENV. As a result, we have investigated the DENV and popular treatment techniques in this research. We have also examined how lipid metabolism, cellular lipids, and lipid receptors affect DENV replication regulation. Lastly, we have looked at how different lipid-lowering medications affect the DENV. This article also discusses the treatment method's future based on its benefits and drawbacks.

Keywords: Cholesterol; Dengue virus; Lipid-lowering drugs; Proprotein convertase subtilisin/kexin type 9 (PCSK9); Statin

DOI: https://doi.org/10.1186/s12985-024-02608-3

BMC Vet Res. 2024 Dec 19. 20(1): 569

Serum metabolic alterations in chickens upon infectious bursal disease virus infection.

Dan Wang, Jiangwei Song, Jing Wang, Rong Quan.

BACKGROUND: Infectious bursal disease virus (IBDV) is a highly contagious immunosuppressive virus of chickens. Chickens acquire infection by the oral route under natural conditions. Although the histological and pathological changes after IBDV infection are well described, the alterations in serum metabolome have not been reported. In this study, SPF chickens were infected with attenuated IBDV (atIBDV) strain LM and very virulent IBDV (vvIBDV) strain LX, respectively. On the seventh day after oral infection, serum samples of experimental chickens were identified using ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS). The serum metabolic profiles were analyzed by multivariate statistical methods. KEGG enrichment analysis was performed to evaluate the dysregulated biological pathways.
RESULTS: We identified 368 significantly altered metabolites in response to both atIBDV and vvIBDV infection. The metabolic disorder of amino acid and lipid was associated with IBDV infection, especially tryptophan, glycerophospholipid, lysine, and tyrosine metabolism. The differential metabolites enriched in the four metabolic pathways were PC(20:4(5Z,8Z,11Z,14Z)/18:0), PE(16:0/18:2(9Z,12Z)), PE(16:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PE(18:0/20:4(5Z,8Z,11Z,14Z)), PE(18:0/20:4(8Z,11Z,14Z,17Z)), PE(18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PE(20:3(8Z,11Z,14Z)/16:0), PE(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:0), PE-NMe(20:5(5Z,8Z,11Z,14Z,17Z)/18:0), PS(20:3(5Z,8Z,11Z)/18:2(9Z,12Z)), 2-aminobenzoic acid, 4-(2-aminophenyl)-2,4-dioxobutanoic acid, N-acetylserotonin, 5-hydroxyindoleacetate, indole-3-acetaldehyde, indole-3-acetate, p-coumaric acid, L-tyrosine, homovanillin, and S-glutaryldihydrolipoamide.
CONCLUSION: The atIBDV and vvIBDV infection causes metabolic changes in chicken serum. The differential metabolites and dysregulated metabolic pathways reflect the host response to the IBDV infection.

Keywords: Infectious bursal disease virus; Metabolic pathway; Serum metabolome

DOI: https://doi.org/10.1186/s12917-024-04402-3

PLoS Pathog. 2024 Dec;20(12): e1012782

Fructose-1,6-diphosphate inhibits viral replication by promoting the lysosomal degradation of HMGB1 and blocking the binding of HMGB1 to the viral genome.

Fructose-1,6-diphosphate (FBP), a key glycolytic metabolite, is recognized for its cytoprotective effects during stress. However, the role of FBP in viral infections is unknown. Here, we demonstrate that virus-infected cells exhibit elevated FBP levels. Exogenous FBP inhibits both RNA and DNA virus infections in vitro and in vivo. Modulating intracellular FBP levels by regulating the expression of the metabolic enzymes FBP1 and PFK1 significantly impacts viral infections. Mechanistically, the inhibitory effects of FBP are not a result of altered viral adhesion or entry and are largely independent of type I interferon-mediated immune responses; rather, they occur through modulation of HMGB1. During viral infections, FBP predominantly reduces the protein levels of HMGB1 by facilitating its lysosomal degradation. Furthermore, FBP interacts with HMGB1 and disrupts the binding of HMGB1 to viral genomes, thereby further inhibiting viral replication. Our findings underscore the potential of FBP as a therapeutic target for controlling viral infections.

DOI: https://doi.org/10.1371/journal.ppat.1012782