bims-mevinf 2023-10-01 papers

Issue of 2023‒10‒01
five papers selected by
Alexander Ivanov, Engelhardt Institute of Molecular Biology

J Neuroinflammation. 2023 Sep 29. 20(1): 218

Metabolic response to CNS infection with flaviviruses.

Marta Dobrzyńska, Anna Moniuszko-Malinowska, Elżbieta Skrzydlewska.

Flaviviruses are arthropod-borne RNA viruses found worldwide that, when introduced into the human body, cause diseases, including neuroinfections, that can lead to serious metabolic consequences and even death. Some of the diseases caused by flaviviruses occur continuously in certain regions, while others occur intermittently or sporadically, causing epidemics. Some of the most common flaviviruses are West Nile virus, dengue virus, tick-borne encephalitis virus, Zika virus and Japanese encephalitis virus. Since all the above-mentioned viruses are capable of penetrating the blood-brain barrier through different mechanisms, their actions also affect the central nervous system (CNS). Like other viruses, flaviviruses, after entering the human body, contribute to redox imbalance and, consequently, to oxidative stress, which promotes inflammation in skin cells, in the blood and in CNS. This review focuses on discussing the effects of oxidative stress and inflammation resulting from pathogen invasion on the metabolic antiviral response of the host, and the ability of viruses to evade the consequences of metabolic changes or exploit them for increased replication and further progression of infection, which affects the development of sequelae and difficulties in therapy.

Keywords: CNS; Flaviviruses; Inflammation; Neuroinfections; Oxidative stress; Viral infections

DOI: https://doi.org/10.1186/s12974-023-02898-4

Viruses. 2023 Sep 14. pii: 1921. [Epub ahead of print]15(9):

microRNA-185 Inhibits SARS-CoV-2 Infection through the Modulation of the Host's Lipid Microenvironment.

Nadine Ahmed, Magen E Francis, Noreen Ahmed, Alyson A Kelvin, John Paul Pezacki.

With the emergence of the novel betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there has been an urgent need for the development of fast-acting antivirals, particularly in dealing with different variants of concern (VOC). SARS-CoV-2, like other RNA viruses, depends on host cell machinery to propagate and misregulate metabolic pathways to its advantage. Herein, we discovered that the immunometabolic microRNA-185 (miR-185) restricts SARS-CoV-2 propagation by affecting its entry and infectivity. The antiviral effects of miR-185 were studied in SARS-CoV-2 Spike protein pseudotyped virus, surrogate virus (HCoV-229E), as well as live SARS-CoV-2 virus in Huh7, A549, and Calu-3 cells. In each model, we consistently observed microRNA-induced reduction in lipid metabolism pathways-associated genes including SREBP2, SQLE, PPARG, AGPAT3, and SCARB1. Interestingly, we also observed changes in angiotensin-converting enzyme 2 (ACE2) levels, the entry receptor for SARS-CoV-2. Taken together, these data show that miR-185 significantly restricts host metabolic and other pathways that appear to be essential to SAR-CoV-2 replication and propagation. Overall, this study highlights an important link between non-coding RNAs, immunometabolic pathways, and viral infection. miR-185 mimics alone or in combination with other antiviral therapeutics represent possible future fast-acting antiviral strategies that are likely to be broadly antiviral against multiple variants as well as different virus types of potential pandemics.

Keywords: Metabolism; SARS-CoV-2; SREBP; antiviral mechanisms; microRNA

DOI: https://doi.org/10.3390/v15091921

J Neuroinflammation. 2023 Sep 27. 20(1): 217

Glycolytic shift during West Nile virus infection provides new therapeutic opportunities.

Patricia Mingo-Casas, Ana-Belén Blázquez, Marta Gómez de Cedrón, Ana San-Félix, Susana Molina, Estela Escribano-Romero, Eva Calvo-Pinilla, Nereida Jiménez de Oya, Ana Ramírez de Molina, Juan-Carlos Saiz, María-Jesús Pérez-Pérez, Miguel A Martín-Acebes.

BACKGROUND: Viral rewiring of host bioenergetics and immunometabolism may provide novel targets for therapeutic interventions against viral infections. Here, we have explored the effect on bioenergetics during the infection with the mosquito-borne flavivirus West Nile virus (WNV), a medically relevant neurotropic pathogen causing outbreaks of meningitis and encephalitis worldwide.RESULTS: A systematic literature search and meta-analysis pointed to a misbalance of glucose homeostasis in the central nervous system of WNV patients. Real-time bioenergetic analyses confirmed upregulation of aerobic glycolysis and a reduction of mitochondrial oxidative phosphorylation during viral replication in cultured cells. Transcriptomics analyses in neural tissues from experimentally infected mice unveiled a glycolytic shift including the upregulation of hexokinases 2 and 3 (Hk2 and Hk3) and pyruvate dehydrogenase kinase 4 (Pdk4). Treatment of infected mice with the Hk inhibitor, 2-deoxy-D-glucose, or the Pdk4 inhibitor, dichloroacetate, alleviated WNV-induced neuroinflammation.
CONCLUSIONS: These results highlight the importance of host energetic metabolism and specifically glycolysis in WNV infection in vivo. This study provides proof of concept for the druggability of the glycolytic pathway for the future development of therapies to combat WNV pathology.

Keywords: Glycolysis; Immunometabolism; Neuroinflammation; West Nile virus

DOI: https://doi.org/10.1186/s12974-023-02899-3

Metabolites. 2023 Aug 22. pii: 968. [Epub ahead of print]13(9):

Metabolic Profiling Early Post-Allogeneic Haematopoietic Cell Transplantation in the Context of CMV Infection.

Kirstine K Rasmussen, Quenia Dos Santos, Cameron Ross MacPherson, Adrian G Zucco, Lars Klingen Gjærde, Emma E Ilett, Isabelle Lodding, Marie Helleberg, Jens D Lundgren, Susanne D Nielsen, Susanne Brix, Henrik Sengeløv, Daniel D Murray.

Immune dysfunction resulting from allogeneic haematopoietic stem cell transplantation (aHSCT) predisposes one to an elevated risk of cytomegalovirus (CMV) infection. Changes in metabolism have been associated with adverse outcomes, and in this study, we explored the associations between metabolic profiles and post-transplantation CMV infection using plasma samples collected 7-33 days after aHSCT. We included 68 aHSCT recipients from Rigshospitalet, Denmark, 50% of whom experienced CMV infection between days 34-100 post-transplantation. First, we investigated whether 12 metabolites selected based on the literature were associated with an increased risk of post-transplantation CMV infection. Second, we conducted an exploratory network-based analysis of the complete metabolic and lipidomic profiles in relation to clinical phenotypes and biological pathways. Lower levels of trimethylamine N-oxide were associated with subsequent CMV infection (multivariable logistic regression: OR = 0.63; 95% CI = [0.41; 0.87]; p = 0.01). Explorative analysis revealed 12 clusters of metabolites or lipids, among which one was predictive of CMV infection, and the others were associated with conditioning regimens, age upon aHSCT, CMV serostatus, and/or sex. Our results provide evidence for an association between the metabolome and CMV infection post-aHSCT that is independent of known risk factors.

Keywords: CMV; TMAO; WGCNA; aHSCT; correlation network analysis; cytomegalovirus; lipidomics; metabolomics

DOI: https://doi.org/10.3390/metabo13090968

Pathogens. 2023 Sep 08. pii: 1146. [Epub ahead of print]12(9):

Host and HBV Interactions and Their Potential Impact on Clinical Outcomes.

Alexis Jose-Abrego, Sonia Roman, Saul Laguna-Meraz, Arturo Panduro.

Hepatitis B virus (HBV) is a challenge for global health services, affecting millions and leading thousands to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. HBV genotyping has revealed unique geographical patterns and relationships with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the human host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

Keywords: HBV genotype H; clinical outcome; hepatitis B virus; immune response; metabolic interaction; viral adaptation

DOI: https://doi.org/10.3390/pathogens12091146