bims-rebvin 2023-03-12 papers

Issue of 2023‒03‒12
four papers selected by
Alexander Ivanov

J Med Virol. 2023 Mar 11.

Viruses and phospholipids: Friends and foes during infection.

Stephanie Rattay, Martin Hufbauer, Peter Hoboth, Martin Sztacho, Baki Akgül.

Viruses have evolved complex and dynamic interactions with their host cells to enable viral replication. In recent years, insights have been gained into the increasingly important role of the host cell lipidome in the life cycle of several viruses. In particular, viruses target phospholipid signaling, synthesis, and metabolism to remodel their host cells into an optimal environment for their replication cycle. Conversely, phospholipids and their associated regulatory enzymes can interfere with viral infection or replication. This review highlights examples of different viruses that illustrate the importance of these diverse virus-phospholipid interactions in different cellular compartments, particularly the role of nuclear phospholipids and their association with human papillomavirus (HPV)-mediated cancer development. This article is protected by copyright. All rights reserved.

Keywords: phospholipids; virus host interactions; virus lipid interactions

DOI: https://doi.org/10.1002/jmv.28658

Ann Hematol. 2023 Mar 11.

G6PD deficiency-does it alter the course of COVID-19 infections?

Tsz Yuen Au, Oskar Wojciech Wiśniewski, Shamiram Benjamin, Tadeusz Kubicki, Dominik Dytfeld, Lidia Gil.

Despite the existence of well-founded data around the relationship between reactive oxygen species (ROS) and glucose-6-phosphate dehydrogenase (G6PD), current research around G6PD-deficient patients with viral infections, and limitations as a result of their condition, are inadequate. Here, we analyze existing data around immunological risks, complications, and consequences of this disease, particularly in relation to COVID-19 infections and treatment. The relationship between G6PD deficiency and elevated ROS leading to increased viral load suggests that these patients may confer heightened infectivity. Additionally, worsened prognoses and more severe complications of infection may be realized in class I G6PD-deficient individuals. Though more research is demanded on the topic, preliminary studies suggest that antioxidative therapy which reduces ROS levels in these patients could prove beneficial in the treatment of viral infections in G6PD-deficient individuals.

Keywords: Antioxidative therapy; COVID-19; G6PD deficiency; Oxidative stress; Viral load

DOI: https://doi.org/10.1007/s00277-023-05164-y

J Neuroinflammation. 2023 Mar 08. 20(1): 61

Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells.

Suelen Silva Gomes Dias, Tamires Cunha-Fernandes, Luciana Souza-Moreira, Vinicius Cardoso Soares, Giselle Barbosa Lima, Isaclaudia G Azevedo-Quintanilha, Julia Santos, Filipe Pereira-Dutra, Caroline Freitas, Patricia A Reis, Stevens Kastrup Rehen, Fernando A Bozza, Thiago M Lopes Souza, Cecilia J G de Almeida, Patricia T Bozza.

Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased expression of lipolysis-associated proteins, leading to significant LD accumulation in human neuroblastoma SH-SY5Y cells and in neural stem cells (NSCs). Pharmacological inhibition of DGAT-1 decreased LD accumulation and ZIKV replication in vitro in human cells and in an in vivo mouse model of infection. In accordance with the role of LDs in the regulation of inflammation and innate immunity, we show that blocking LD formation has major roles in inflammatory cytokine production in the brain. Moreover, we observed that inhibition of DGAT-1 inhibited the weight loss and mortality induced by ZIKV infection in vivo. Our results reveal that LD biogenesis triggered by ZIKV infection is a crucial step for ZIKV replication and pathogenesis in neural cells. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development.

Keywords: Immunometabolism; Inflammation; Lipid droplets; Lipid metabolism; Neuroinfection; Zika virus

DOI: https://doi.org/10.1186/s12974-023-02736-7

Int J Mol Sci. 2023 Feb 23. pii: 4427. [Epub ahead of print]24(5):

Transcriptomes of Zebrafish in Early Stages of Multiple Viral Invasions Reveal the Role of Sterols in Innate Immune Switch-On.

Gang Ouyang, Le Yuan, Xiao-Qin Xia, Wanting Zhang, Mijuan Shi.

Although it is widely accepted that in the early stages of virus infection, fish pattern recognition receptors are the first to identify viruses and initiate innate immune responses, this process has never been thoroughly investigated. In this study, we infected larval zebrafish with four different viruses and analyzed whole-fish expression profiles from five groups of fish, including controls, at 10 h after infection. At this early stage of virus infection, 60.28% of the differentially expressed genes displayed the same expression pattern across all viruses, with the majority of immune-related genes downregulated and genes associated with protein synthesis and sterol synthesis upregulated. Furthermore, these protein synthesis- and sterol synthesis-related genes were strongly positively correlated in the expression pattern of the rare key upregulated immune genes, IRF3 and IRF7, which were not positively correlated with any known pattern recognition receptor gene. We hypothesize that viral infection triggered a large amount of protein synthesis that stressed the endoplasmic reticulum and the organism responded to this stress by suppressing the body's immune system while also mediating an increase in steroids. The increase in sterols then participates the activation of IRF3 and IRF7 and triggers the fish's innate immunological response to the virus infection.

Keywords: early stage of viral infection; steroids; stress; switch-on innate immune

DOI: https://doi.org/10.3390/ijms24054427