bims-mevinf 2024-05-26 papers

bims-mevinf

Biomed News

on Metabolism in viral infections

Issue of 2024–05–26
twelve papers selected by
Alexander Ivanov, Engelhardt Institute of Molecular Biology

NRF2-mediated regulation of lipid pathways in viral infection.
Decoding macrophage immunometabolism in human viral infection.
Insights into the Activation of Unfolded Protein Response Mechanism during Coronavirus Infection.
An Overview of the Unfolded Protein Response (UPR) and Autophagy Pathways in Human Viral Oncogenesis.
Viral Infection Leads to a Unique Suite of Allelopathic Chemical Signals in Three Diatom Host-Virus Pairs.
Hyperglycemia facilitates EV71 replication: Insights into miR-206-mediated regulation of G3BP2 promoting EV71 IRES activity.
Nanomedicine-mediated recovery of antioxidant glutathione peroxidase activity after oxidative-stress cellular damage: Insights for neurological long COVID.
VEEV TC-83 Triggers Dysregulation of the Tryptophan-Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice.
Exploring free amino acid profiles in Crimean-Congo hemorrhagic fever patients: Implications for disease progression.
Transmissible gastroenteritis virus induces inflammatory responses via RIG-I/NF-κB/HIF-1α/glycolysis axis in intestinal organoids and in vivo.
Cholesterol Modulation Attenuates the AD-like Phenotype Induced by Herpes Simplex Virus Type 1 Infection.
The immune response to RNA suppresses nucleic acid synthesis by limiting ribose 5-phosphate.

Mol Aspects Med. 2024 May 20. pii: S0098-2997(24)00038-4. [Epub ahead of print]97 101279

NRF2-mediated regulation of lipid pathways in viral infection.

Khursheed Muzammil, Zahraa Sabah Ghnim, Ibrahim Saeed Gataa, Ali Fawzi Al-Hussainy, Nashat Ali Soud, Mohaned Adil, Mohammed Ali Shallan, Saman Yasamineh.

  The first line of defense against viral infection of the host cell is the cellular lipid membrane, which is also a crucial first site of contact for viruses. Lipids may sometimes be used as viral receptors by viruses. For effective infection, viruses significantly depend on lipid rafts during the majority of the viral life cycle. It has been discovered that different viruses employ different lipid raft modification methods for attachment, internalization, membrane fusion, genome replication, assembly, and release. To preserve cellular homeostasis, cells have potent antioxidant, detoxifying, and cytoprotective capabilities. Nuclear factor erythroid 2-related factor 2 (NRF2), widely expressed in many tissues and cell types, is one crucial component controlling electrophilic and oxidative stress (OS). NRF2 has recently been given novel tasks, including controlling inflammation and antiviral interferon (IFN) responses. The activation of NRF2 has two effects: it may both promote and prevent the development of viral diseases. NRF2 may also alter the host's metabolism and innate immunity during viral infection. However, its primary function in viral infections is to regulate reactive oxygen species (ROS). In several research, the impact of NRF2 on lipid metabolism has been examined. NRF2 is also involved in the control of lipids during viral infection. We evaluated NRF2's function in controlling viral and lipid infections in this research. We also looked at how lipids function in viral infections. Finally, we investigated the role of NRF2 in lipid modulation during viral infections.

Keywords:  Antioxidant; Lipid; NRF2; Viral infection

DOI:  https://doi.org/10.1016/j.mam.2024.101279
Adv Protein Chem Struct Biol. 2024 ;pii: S1876-1623(23)00107-4. [Epub ahead of print]140 493-523

Decoding macrophage immunometabolism in human viral infection.

Takhellambam Malemnganba, Aditi Rattan, Vijay Kumar Prajapati.

  Immune-metabolic interactions play a pivotal role in both host defense and susceptibility to various diseases. Immunometabolism, an interdisciplinary field, seeks to elucidate how metabolic processes impact the immune system. In the context of viral infections, macrophages are often exploited by viruses for their replication and propagation. These infections trigger significant metabolic reprogramming within macrophages and polarization of distinct M1 and M2 phenotypes. This metabolic reprogramming involves alterations in standard- pathways such as the Krebs cycle, glycolysis, lipid metabolism, the pentose phosphate pathway, and amino acid metabolism. Disruptions in the balance of key intermediates like spermidine, itaconate, and citrate within these pathways contribute to the severity of viral diseases. In this chapter, we describe the manipulation of metabolic pathways by viruses and how they crosstalk between signaling pathways to evade the immune system. This intricate interplay often involves the upregulation or downregulation of specific metabolites, making these molecules potential biomarkers for diseases like HIV, HCV, and SARS-CoV. Techniques such as Nuclear Magnetic Resonance (NMR) and Mass Spectrometry, are the evaluative ways to analyze these metabolites. Considering the importance of macrophages in the inflammatory response, addressing their metabolome holds great promise for the creating future therapeutic targets aimed at combating a wide spectrum of viral infections.

Keywords:  Cellular cross-talk; Immunometabolism; Macrophages; Metabolic reprogramming; Viral infection

DOI:  https://doi.org/10.1016/bs.apcsb.2023.12.003
Curr Issues Mol Biol. 2024 May 05. 46(5): 4286-4308

Insights into the Activation of Unfolded Protein Response Mechanism during Coronavirus Infection.

Panagiotis Keramidas, Maria Pitou, Eleni Papachristou, Theodora Choli-Papadopoulou.

  Coronaviruses represent a significant class of viruses that affect both animals and humans. Their replication cycle is strongly associated with the endoplasmic reticulum (ER), which, upon virus invasion, triggers ER stress responses. The activation of the unfolded protein response (UPR) within infected cells is performed from three transmembrane receptors, IRE1, PERK, and ATF6, and results in a reduction in protein production, a boost in the ER's ability to fold proteins properly, and the initiation of ER-associated degradation (ERAD) to remove misfolded or unfolded proteins. However, in cases of prolonged and severe ER stress, the UPR can also instigate apoptotic cell death and inflammation. Herein, we discuss the ER-triggered host responses after coronavirus infection, as well as the pharmaceutical targeting of the UPR as a potential antiviral strategy.

Keywords:  ATF6; CoV; ER stress; IRE1; PERK; coronavirus; pharmacological inhibition; unfolded protein response

DOI:  https://doi.org/10.3390/cimb46050261
Int Rev Cell Mol Biol. 2024 ;pii: S1937-6448(24)00014-5. [Epub ahead of print]386 81-131

An Overview of the Unfolded Protein Response (UPR) and Autophagy Pathways in Human Viral Oncogenesis.

Shovan Dutta, Anirban Ganguly, Sounak Ghosh Roy.

  Autophagy and Unfolded Protein Response (UPR) can be regarded as the safe keepers of cells exposed to intense stress. Autophagy maintains cellular homeostasis, ensuring the removal of foreign particles and misfolded macromolecules from the cytoplasm and facilitating the return of the building blocks into the system. On the other hand, UPR serves as a shock response to prolonged stress, especially Endoplasmic Reticulum Stress (ERS), which also includes the accumulation of misfolded proteins in the ER. Since one of the many effects of viral infection on the host cell machinery is the hijacking of the host translational system, which leaves in its wake a plethora of misfolded proteins in the ER, it is perhaps not surprising that UPR and autophagy are common occurrences in infected cells, tissues, and patient samples. In this book chapter, we try to emphasize how UPR, and autophagy are significant in infections caused by six major oncolytic viruses-Epstein-Barr (EBV), Human Papilloma Virus (HPV), Human Immunodeficiency Virus (HIV), Human Herpesvirus-8 (HHV-8), Human T-cell Lymphotropic Virus (HTLV-1), and Hepatitis B Virus (HBV). Here, we document how whole-virus infection or overexpression of individual viral proteins in vitro and in vivo models can regulate the different branches of UPR and the various stages of macro autophagy. As is true with other viral infections, the relationship is complicated because the same virus (or the viral protein) exerts different effects on UPR and Autophagy. The nature of this response is determined by the cell types, or in some cases, the presence of diverse extracellular stimuli. The vice versa is equally valid, i.e., UPR and autophagy exhibit both anti-tumor and pro-tumor properties based on the cell type and other factors like concentrations of different metabolites. Thus, we have tried to coherently summarize the existing knowledge, the crux of which can hopefully be harnessed to design vaccines and therapies targeted at viral carcinogenesis.

Keywords:  ATF6; Autophagy; CHOP; EBV; ERS; HHV-8; HIV; HPV; HTLV-1; IRE1-α; PERK; UPR

DOI:  https://doi.org/10.1016/bs.ircmb.2024.01.004
Mar Drugs. 2024 May 17. pii: 228. [Epub ahead of print]22(5):

Viral Infection Leads to a Unique Suite of Allelopathic Chemical Signals in Three Diatom Host-Virus Pairs.

Bethanie R Edwards, Kimberlee Thamatrakoln, Helen F Fredricks, Kay D Bidle, Benjamin A S Van Mooy.

  Ecophysiological stress and the grazing of diatoms are known to elicit the production of chemical defense compounds called oxylipins, which are toxic to a wide range of marine organisms. Here we show that (1) the viral infection and lysis of diatoms resulted in oxylipin production; (2) the suite of compounds produced depended on the diatom host and the infecting virus; and (3) the virus-mediated oxylipidome was distinct, in both magnitude and diversity, from oxylipins produced due to stress associated with the growth phase. We used high-resolution accurate-mass mass spectrometry to observe changes in the dissolved lipidome of diatom cells infected with viruses over 3 to 4 days, compared to diatom cells in exponential, stationary, and decline phases of growth. Three host virus pairs were used as model systems: Chaetoceros tenuissimus infected with CtenDNAV; C. tenuissimus infected with CtenRNAV; and Chaetoceros socialis infected with CsfrRNAV. Several of the compounds that were significantly overproduced during viral infection are known to decrease the reproductive success of copepods and interfere with microzooplankton grazing. Specifically, oxylipins associated with allelopathy towards zooplankton from the 6-, 9-, 11-, and 15-lipogenase (LOX) pathways were significantly more abundant during viral lysis. 9-hydroperoxy hexadecatetraenoic acid was identified as the strongest biomarker for the infection of Chaetoceros diatoms. C. tenuissimus produced longer, more oxidized oxylipins when lysed by CtenRNAV compared to CtenDNAV. However, CtenDNAV caused a more statistically significant response in the lipidome, producing more oxylipins from known diatom LOX pathways than CtenRNAV. A smaller set of compounds was significantly more abundant in stationary and declining C. tenuissimus and C. socialis controls. Two allelopathic oxylipins in the 15-LOX pathway and essential fatty acids, arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were more abundant in the stationary phase than during the lysis of C. socialis. The host-virus pair comparisons underscore the species-level differences in oxylipin production and the value of screening more host-virus systems. We propose that the viral infection of diatoms elicits chemical defense via oxylipins which deters grazing with downstream trophic and biogeochemical effects.

Keywords:  allelopathy; chemical signaling; diatom viruses; dissolved organic matter; lipid; lipidomics; marine virology; orbitrap mass spectrometry; oxylipins; viral ecology

DOI:  https://doi.org/10.3390/md22050228
Theranostics. 2024 ;14(7): 2706-2718

Hyperglycemia facilitates EV71 replication: Insights into miR-206-mediated regulation of G3BP2 promoting EV71 IRES activity.

Rai-Hua Lai, Yen-Hung Chow, Yi-Wen Lin, Nai-Hsiang Chung, Shu-Wei Nien, Jyh-Lyh Juang.

  Background: Neurotropic virus infections actively manipulate host cell metabolism to enhance virus neurovirulence. Although hyperglycemia is common during severe infections, its specific role remains unclear. This study investigates the impact of hyperglycemia on the neurovirulence of enterovirus 71 (EV71), a neurovirulent virus relying on internal ribosome entry site (IRES)-mediated translation for replication. Methods: Utilizing hSCARB2-transgenic mice, we explore the effects of hyperglycemia in EV71 infection and elucidate the underlying mechanisms. Results: Remarkably, administering insulin alone to reduce hyperglycemia in hSCARB2-transgenic mice results in a decrease in brainstem encephalitis and viral load. Conversely, induced hyperglycemia exacerbates neuropathogenesis, highlighting the pivotal role of hyperglycemia in neurovirulence. Notably, miR-206 emerges as a crucial mediator induced by viral infection, with its expression further heightened by hyperglycemia and concurrently repressed by insulin. The use of antagomiR-206 effectively mitigates EV71-induced brainstem encephalitis and reduces viral load. Mechanistically, miR-206 facilitates IRES-driven virus replication by repressing the stress granule protein G3BP2. Conclusions: Novel therapeutic approaches against severe EV71 infections involve managing hyperglycemia and targeting the miR-206-stress granule pathway to modulate virus IRES activity.

Keywords:  enterovirus; hyperglycemia; internal ribosome entry site (IRES); miR-206; neurovirulence

DOI:  https://doi.org/10.7150/thno.93883
J Med Virol. 2024 May;96(5): e29680

Nanomedicine-mediated recovery of antioxidant glutathione peroxidase activity after oxidative-stress cellular damage: Insights for neurological long COVID.

Thelma Akanchise, Borislav Angelov, Angelina Angelova.

  Nanomedicine for treating post-viral infectious disease syndrome is at an emerging stage. Despite promising results from preclinical studies on conventional antioxidants, their clinical translation as a therapy for treating post-COVID conditions remains challenging. The limitations are due to their low bioavailability, instability, limited transport to the target tissues, and short half-life, requiring frequent and high doses. Activating the immune system during coronavirus (SARS-CoV-2) infection can lead to increased production of reactive oxygen species (ROS), depleted antioxidant reserve, and finally, oxidative stress and neuroinflammation. To tackle this problem, we developed an antioxidant nanotherapy based on lipid (vesicular and cubosomal types) nanoparticles (LNPs) co-encapsulating ginkgolide B and quercetin. The antioxidant-loaded nanocarriers were prepared by a self-assembly method via hydration of a lyophilized mixed thin lipid film. We evaluated the LNPs in a new in vitro model for studying neuronal dysfunction caused by oxidative stress in coronavirus infection. We examined the key downstream signaling pathways that are triggered in response to potassium persulfate (KPS) causing oxidative stress-mediated neurotoxicity. Treatment of neuronally-derived cells (SH-SY5Y) with KPS (50 mM) for 30 min markedly increased mitochondrial dysfunction while depleting the levels of both glutathione peroxidase (GSH-Px) and tyrosine hydroxylase (TH). This led to the sequential activation of apoptotic and necrotic cell death processes, which corroborates with the crucial implication of the two proteins (GSH-Px and TH) in the long-COVID syndrome. Nanomedicine-mediated treatment with ginkgolide B-loaded cubosomes and vesicular LNPs showed minimal cytotoxicity and completely attenuated the KPS-induced cell death process, decreasing apoptosis from 32.6% (KPS) to 19.0% (MO-GB), 12.8% (MO-GB-Quer), 14.8% (DMPC-PEG-GB), and 23.6% (DMPC-PEG-GB-Quer) via free radical scavenging and replenished GSH-Px levels. These findings indicated that GB-LNPs-based nanomedicines may protect against KPS-induced apoptosis by regulating intracellular redox homeostasis.

Keywords:  ginkgolide B; glutathione peroxidase; long COVID syndrome; nanomedicine; oxidative stress; quercetin

DOI:  https://doi.org/10.1002/jmv.29680
Pathogens. 2024 May 09. pii: 397. [Epub ahead of print]13(5):

VEEV TC-83 Triggers Dysregulation of the Tryptophan-Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice.

Chanida Fongsaran, Kelly T Dineley, Slobodan Paessler, Irma E Cisneros.

  Neurodegenerative diseases are chronic conditions affecting the central nervous system (CNS). Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid beta in the limbic and cortical brain regions. AD is presumed to result from genetic abnormalities or environmental factors, including viral infections, which may have deleterious, long-term effects. In this study, we demonstrate that the Venezuelan equine encephalitis virus (VEEV) commonly induces neurodegeneration and long-term neurological or cognitive sequelae. Notably, the effects of VEEV infection can persistently influence gene expression in the mouse brain, suggesting a potential link between the observed neurodegenerative outcomes and long-term alterations in gene expression. Additionally, we show that alphavirus encephalitis exacerbates the neuropathological profile of AD through crosstalk between inflammatory and kynurenine pathways, generating a range of metabolites with potent effects. Using a mouse model for β-amyloidosis, Tg2576 mice, we found that cognitive deficits and brain pathology were more severe in Tg2576 mice infected with VEEV TC-83 compared to mock-infected controls. Thus, during immune activation, the kynurenine pathway plays a more active role in the VEEV TC-83-infected cells, leading to increases in the abundance of transcripts related to the kynurenine pathway of tryptophan metabolism. This pathway generates several metabolites with potent effects on neurotransmitter systems as well as on inflammation, as observed in VEEV TC-83-infected animals.

Keywords:  Alzheimer’s disease; TC-83; indoleamine 2,3-dioxygenase; neurodegeneration; neuroinflammation; quinolinic acid

DOI:  https://doi.org/10.3390/pathogens13050397
J Med Virol. 2024 May;96(5): e29637

Exploring free amino acid profiles in Crimean-Congo hemorrhagic fever patients: Implications for disease progression.

Seyit Ali Büyüktuna, Serra İlayda Yerlitaş, Gözde Ertük Zararsız, Kübra Doğan, Demet Kablan, Gökhan Bağcı, Selda Özer, Cihad Baysal, Yasemin Çakır, Ahu Cephe, Necla Koçhan, Gökmen Zararız, Halef Okan Doğan.

  This study investigated the intricate interplay between Crimean-Congo hemorrhagic fever virus infection and alterations in amino acid metabolism. The primary aim is to elucidate the impact of Crimean-Congo hemorrhagic fever (CCHF) on specific amino acid concentrations and identify potential metabolic markers associated with viral infection. One hundred ninety individuals participated in this study, comprising 115 CCHF patients, 30 CCHF negative patients, and 45 healthy controls. Liquid chromatography-tandem mass spectrometry techniques were employed to quantify amino acid concentrations. The amino acid metabolic profiles in CCHF patients exhibit substantial distinctions from those in the control group. Patients highlight distinct metabolic reprogramming, notably characterized by arginine, histidine, taurine, glutamic acid, and glutamine metabolism shifts. These changes have been associated with the underlying molecular mechanisms of the disease. Exploring novel therapeutic and diagnostic strategies addressing specific amino acids may offer potential means to mitigate the severity of the disease.

Keywords:  Amino acid; Crimean‐Congo hemorrhagic fever; LC‐MS/MS; severity

DOI:  https://doi.org/10.1002/jmv.29637
J Virol. 2024 May 23. e0046124

Transmissible gastroenteritis virus induces inflammatory responses via RIG-I/NF-κB/HIF-1α/glycolysis axis in intestinal organoids and in vivo.

Yunhang Zhang, Ning Yang, Yang Li, Chen Tan, Yifei Cai, Xue Rui, Yuanyuan Liu, Yuguang Fu, Guangliang Liu.

  Transmissible gastroenteritis virus (TGEV)-induced enteritis is characterized by watery diarrhea, vomiting, and dehydration, and has high mortality in newborn piglets, resulting in significant economic losses in the pig industry worldwide. Conventional cell lines have been used for many years to investigate inflammation induced by TGEV, but these cell lines may not mimic the actual intestinal environment, making it difficult to obtain accurate results. In this study, apical-out porcine intestinal organoids were employed to study TEGV-induced inflammation. We found that apical-out organoids were susceptible to TGEV infection, and the expression of representative inflammatory cytokines was significantly upregulated upon TGEV infection. In addition, retinoic acid-inducible gene I (RIG-I) and the nuclear factor-kappa B (NF-κB) pathway were responsible for the expression of inflammatory cytokines induced by TGEV infection. We also discovered that the transcription factor hypoxia-inducible factor-1α (HIF-1α) positively regulated TGEV-induced inflammation by activating glycolysis in apical-out organoids, and pig experiments identified the same molecular mechanism as the ex vivo results. Collectively, we unveiled that the inflammatory responses induced by TGEV were modulated via the RIG-I/NF-κB/HIF-1α/glycolysis axis ex vivo and in vivo. This study provides novel insights into TGEV-induced enteritis and verifies intestinal organoids as a reliable model for investigating virus-induced inflammation.
IMPORTANCE: Intestinal organoids are a newly developed culture system for investigating immune responses to virus infection. This culture model better represents the physiological environment compared with well-established cell lines. In this study, we discovered that inflammatory responses induced by TGEV infection were regulated by the RIG-I/NF-κB/HIF-1α/glycolysis axis in apical-out porcine organoids and in pigs. Our findings contribute to understanding the mechanism of intestinal inflammation upon viral infection and highlight apical-out organoids as a physiological model to mimic virus-induced inflammation.

Keywords:  HIF-1α; NF-κB; TGEV; apical-out intestinal organoids; inflammation

DOI:  https://doi.org/10.1128/jvi.00461-24
Biomolecules. 2024 May 20. pii: 603. [Epub ahead of print]14(5):

Cholesterol Modulation Attenuates the AD-like Phenotype Induced by Herpes Simplex Virus Type 1 Infection.

Blanca Salgado, Beatriz Izquierdo, Alba Zapata, Isabel Sastre, Henrike Kristen, Julia Terreros, Víctor Mejías, María J Bullido, Jesús Aldudo.

  Cholesterol, a crucial component of cell membranes, influences various biological processes, including membrane trafficking, signal transduction, and host-pathogen interactions. Disruptions in cholesterol homeostasis have been linked to congenital and acquired conditions, including neurodegenerative disorders such as Alzheimer's disease (AD). Previous research from our group has demonstrated that herpes simplex virus type I (HSV-1) induces an AD-like phenotype in several cell models of infection. This study explores the interplay between cholesterol and HSV-1-induced neurodegeneration. The impact of cholesterol was determined by modulating its levels with methyl-beta-cyclodextrin (MβCD) using the neuroblastoma cell lines SK-N-MC and N2a. We have found that HSV-1 infection triggers the intracellular accumulation of cholesterol in structures resembling endolysosomal/autophagic compartments, a process reversible upon MβCD treatment. Moreover, MβCD exhibits inhibitory effects at various stages of HSV-1 infection, underscoring the importance of cellular cholesterol levels, not only in the viral entry process but also in subsequent post-entry stages. MβCD also alleviated several features of AD-like neurodegeneration induced by viral infection, including lysosomal impairment and intracellular accumulation of amyloid-beta peptide (Aβ) and phosphorylated tau. In conclusion, these findings highlight the connection between cholesterol, neurodegeneration, and HSV-1 infection, providing valuable insights into the underlying mechanisms of AD.

Keywords:  Alzheimer’s disease; HSV-1; beta-amyloid; cholesterol; hyperphosphorylated tau; infection; lysosomal alterations; methyl-beta-cyclodextrin; neuroblastoma cells; neurodegeneration

DOI:  https://doi.org/10.3390/biom14050603
EMBO J. 2024 May 22.

The immune response to RNA suppresses nucleic acid synthesis by limiting ribose 5-phosphate.

Pushpak Bhattacharjee, Die Wang, Dovile Anderson, Joshua N Buckler, Eveline de Geus, Feng Alex Yan, Galina Polekhina, Ralf Schittenhelm, Darren J Creek, Lawrence D Harris, Anthony J Sadler.

  During infection viruses hijack host cell metabolism to promote their replication. Here, analysis of metabolite alterations in macrophages exposed to poly I:C recognises that the antiviral effector Protein Kinase RNA-activated (PKR) suppresses glucose breakdown within the pentose phosphate pathway (PPP). This pathway runs parallel to central glycolysis and is critical to producing NADPH and pentose precursors for nucleotides. Changes in metabolite levels between wild-type and PKR-ablated macrophages show that PKR controls the generation of ribose 5-phosphate, in a manner distinct from its established function in gene expression but dependent on its kinase activity. PKR phosphorylates and inhibits the Ribose 5-Phosphate Isomerase A (RPIA), thereby preventing interconversion of ribulose- to ribose 5-phosphate. This activity preserves redox control but decreases production of ribose 5-phosphate for nucleotide biosynthesis. Accordingly, the PKR-mediated immune response to RNA suppresses nucleic acid production. In line, pharmacological targeting of the PPP during infection decreases the replication of the Herpes simplex virus. These results identify an immune response-mediated control of host cell metabolism and suggest targeting the RPIA as a potential innovative antiviral treatment.

Keywords:  Antiviral; Immunity; Metabolism; Nucleotide Biosynthesis; PKR (Protein Kinase RNA-Activated); PPP (Pentose Phosphate Pathway); RPIA (Ribose 5-Phosphate Isomerase A)

DOI:  https://doi.org/10.1038/s44318-024-00100-w