bims-mevinf 2025-03-30 papers

bims-mevinf

Biomed News

on Metabolism in viral infections

Issue of 2025–03–30
twelve papers selected by
Alexander Ivanov, Engelhardt Institute of Molecular Biology

Enterovirus A71-induced glycolysis is essential for viral replication by activating PI3K/Akt pathway.
The long noncoding RNA APR attenuates PPRV infection-induced accumulation of intracellular iron to inhibit membrane lipid peroxidation and viral replication.
Role of endoplasmic reticulum stress in cell apoptosis induced by duck hepatitis A virus type 1 infection.
The interaction of Orthoflavivirus nonstructural proteins 3 and 5 with human fatty acid synthase.
Plasma lipidomic alterations during pathogenic SIV infection with and without antiretroviral therapy.
Modulation of Ire1-Xbp1 Defense Pathway in Encephalomyocarditis Virus-Infected HeLa Cells.
1H NMR Urinary Metabolomics Profiling of Newborns with Congenital Human Cytomegalovirus Infection: Insights into Metabolic Alterations.
Oxidative stress in the liver of chicken during fowl adenovirus serotype 4 infection.
Analyses of Saliva Metabolome Reveal Patterns of Metabolites That Differentiate SARS-CoV-2 Infection and COVID-19 Disease Severity.
Impact of metformin on HBV replication: No evidence of suppression in vitro.
Do Statins Affect Viral Infections Encountered by International Travelers?
Turkey B Cell Transcriptome Profile During Turkey Hemorrhagic Enteritis Virus (THEV) Infection Highlights Upregulated Apoptosis and Breakdown Pathways That May Mediate Immunosuppression.

Microb Pathog. 2025 Mar 22. pii: S0882-4010(25)00230-X. [Epub ahead of print]203 107505

Enterovirus A71-induced glycolysis is essential for viral replication by activating PI3K/Akt pathway.

Dan Li, Jing Yang, Yi Shen, Meng Su, Wenyi Ma, Wenping Guo, Jiangli Wang, Xiaohui Zou, Guangcheng Xie.

  Enterovirus A71 (EV-A71), an obligate intracellular acellular microbe, depends entirely on host cellular metabolism to accomplish viral replication. Glycolysis is a glucose metabolic pathway that generates adenosine triphosphate (ATP) and other intermediates that activate other metabolic pathways. However, the role of glycolysis in EV-A71 replication remains unknown. In this study, we systematically investigated the role and regulation of glycolysis in human tonsillar epithelial cells (HTECs) during EV-A71 infection. Concentration of glucose was decreased, the glucose-6-phosphate (G6P) level and lactate production were increased with upregulating the glucose transporter1 (Glut1) expression in EV-A71-infected HTECs. Moreover, cellular metabolism, including glycolysis, pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and cellular respiration were activated. PI3K/Akt pathway was also activated by EV-A71. Concentration of glucose was significantly increased but concentrations of G6P and lactate were significantly decreased along with decreased Glut1 protein level, and EV-A71 replication was also significantly suppressed when the glycolysis was inhibited by 2-deoxy-D-glucose (2DG) and sodium oxamate (Oxamate) treatments. A time-of-addition assay revealed that glycolysis regulated EV-A71 replication at the early (attachment/entry) and late (release) stages of the EV-A71 life cycle. Addition of glucose or lactate experiments showed too low or too high concentrations of glucose and excessive lactate impaired EV-A71 replication by decreasing Glut1 expression to inhibit glycolysis. Inhibition of oxidative phosphorylation (OXPHOS) also decreased EV-A71 replication. Finally, PI3K/Akt pathway inhibition severely reduced EV-A71 replication and G6P production. Therefore, these findings indicate that EV-A71 alters the host cellular metabolism to facilitate viral replication by exploiting glycolysis via the PI3K/Akt pathway, thereby providing a novel insight into the interaction between EV-A71 and host cells.

Keywords:  Cellular metabolism; Enterovirus A71; Glucose-6-phosphate; Glycolysis; PI3K/Akt pathway

DOI:  https://doi.org/10.1016/j.micpath.2025.107505
mBio. 2025 Mar 24. e0012725

The long noncoding RNA APR attenuates PPRV infection-induced accumulation of intracellular iron to inhibit membrane lipid peroxidation and viral replication.

Bo Wen, Wenchi Chang, Lulu Yang, Daiyue Lv, Lizhen Wang, Lei Wang, Yanzhao Xu, Jianhe Hu, Ke Ding, Qinghong Xue, Xuefeng Qi, Bo Yang, Jingyu Wang.

  Peste des petits ruminants virus (PPRV) is an important pathogen that has long been a significant threat to small ruminant productivity worldwide. Iron metabolism is vital to the host and the pathogen. However, the mechanism underlying host-PPRV interactions from the perspective of iron metabolism and iron-mediated membrane lipid peroxidation has not been reported thus far. In this study, we identified a novel host long-noncoding RNA (lncRNA), APR, that impairs PPRV infectivity by sponging miR-3955-5p, a negative microRNA (miRNA) that directly targets the gene encoding the ferritin-heavy chain 1 (FTH1) protein. Importantly, we demonstrated that PPRV infection causes aberrant cellular iron accumulation by increasing transferrin receptor (TFRC) expression and that iron accumulation induces reticulophagy and ferroptosis, which benefits PPRV replication. Moreover, PPRV infection enhanced the localization of cellular iron on the endoplasmic reticulum (ER) and caused ER membrane damage by promoting excess lipid peroxidation to induce reticulophagy. Interestingly, APR decreased PPRV infection-induced accumulation of intracellular Fe2+ via miR-3955-5p/FTH1 axis and ultimately inhibited reticulophagy and ferroptosis. Additionally, our results indicate that interferon regulatory factor 1 promotes APR transcription by positively regulating APR promoter activity after PPRV infection. Taken together, our findings revealed a new pattern of PPRV-host interactions, involving noncoding RNA regulation, iron metabolism, and iron-related membrane lipid peroxidation, which is critical for understanding the host defense against PPRV infection and the pathogenesis of PPRV.IMPORTANCEMany viruses have been demonstrated to engage in iron metabolism to facilitate their replication and pathogenesis. However, the mechanism by which PPRV interacts with host cells from the perspective of iron metabolism, or iron-mediated membrane lipid peroxidation, has not yet been reported. Our data provide the first direct evidence that PPRV infection induces aberrant iron accumulation to promote viral replication and reveal a novel host lncRNA, APR, as a regulator of iron accumulation by promoting FTH1 protein expression. In this study, PPRV infection increased cellular iron accumulation by increasing TFRC expression, and more importantly, iron overload increased viral infectivity as well as promoted ER membrane lipid peroxidation by enhancing the localization of cellular iron on the ER and ultimately induced ferroptosis and reticulophagy. Furthermore, a host factor, the lncRNA APR, was found to decrease cellular iron accumulation by sponging miR-3955-5p, which directly targets the gene encoding the FTH1 protein, thereby attenuating PPRV infection-induced ferroptosis and reticulophagy and inhibiting PPRV infection. Taken together, the results of the present study provide new insight into our understanding of host-PPRV interaction and pathogenesis from the perspective of iron metabolism and reveal potential targets for therapeutics against PPRV infection.

Keywords:  PPRV; iron overload; lipid peroxidation; lncRNA APR; replication

DOI:  https://doi.org/10.1128/mbio.00127-25
Front Immunol. 2025 ;16 1567540

Role of endoplasmic reticulum stress in cell apoptosis induced by duck hepatitis A virus type 1 infection.

Jingjing Lan, Ruihua Zhang, Guige Xu, Hui Yan, Jingyu Wang, Xingxing Shi, Yanli Zhu, Zhijing Xie, Shijin Jiang.

  The endoplasmic reticulum (ER), an elaborate cellular organelle that interweaves the cytosol, nucleus, mitochondria and plasma membrane, is essential for cell function and survival. Disruption of ER function can trigger unfolded protein response (UPR), which is activated by ER stress (ERS). In this study, we investigated the role of ERS in cell apoptosis induced by duck hepatitis A virus type 1 (DHAV-1) infection. Our findings revealed that DHAV-1 infection led to the activation of ERS. Specially, the expression of glucose-regulated protein 78 (GRP78) was upregulated, activating two pathways of UPR: the protein kinase R-like ER kinase (PERK) pathway and the inositol-requiring enzyme 1(IRE1) pathway. Consequently, phosphorylation of eukaryotic initiation factor 2 alpha (p-eIF2α) was increased, and transcription factor 4 (ATF4) was up-regulated, resulting in the induction of the apoptotic C/EBP homologous protein (CHOP). DHAV-1-infected cells exhibited various apoptotic phenotypes, including growth arrest, induction of the DNA damage-inducible protein 34 (GADD34), activation of caspase-3, and suppression of antiapoptotic protein B cell lymphoma-2 (Bcl-2). Importantly, inhibition of PERK or protein kinase R (PKR) activity suppressed CHOP activation and DHAV-1 replication, indicating that the PERK/PKR-eIF2α pathway played a crucial role in ERS-induced apoptosis. Collectively, our study provides novel insights into the mechanism of DHAV-1-induced apoptosis and reveals a potential defense mechanism against DHAV-1 replication.

Keywords:  CHOP; DHAV-1; ERS; UPR; apoptosis

DOI:  https://doi.org/10.3389/fimmu.2025.1567540
PLoS One. 2025 ;20(3): e0319207

The interaction of Orthoflavivirus nonstructural proteins 3 and 5 with human fatty acid synthase.

Suthatta Sornprasert, Wannapa Sornjai, Duncan R Smith.

Mosquito-transmitted viruses of the genus Orthoflavivirus impose a significant public health burden in many tropical and sub-tropical countries around the world, yet there is still no therapeutic drug to treat infection by any of these viruses, and so a deeper understanding of the mechanism of viral replication is required to identify potential therapeutic targets. Studies have shown that lipid metabolism is modulated upon virus infection, and that fatty acid synthase (FASN) is a key enzyme in fatty acid biosynthesis. In particular it has been reported that FASN interacts with DENV NS3 and is subsequently located to the replication complex. To further investigate this, the interaction of FASN with NS3 and NS5 of the Orthoflaviviruses dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) was investigated by coimmunoprecipitation and indirect immunofluorescent assay. Unexpectedly, FASN interacted with both NS3 and NS5 independently. The colocalization of NS3 and FASN was found for all investigated viruses, and while NS5 interacted with FASN, colocalization was not observed. Markedly however, FASN colocalized with dsRNA, a marker for the replication complex. FASN is an essential enzyme and plays a role in viral replication complex and cellular membrane remodelling. The interaction of FASN with both NS3 and NS5, as well as some of FASN being localized to the site of replication for DENV, JEV and ZIKV further highlights FASN as an important therapeutic target which may have applications to many mosquito-transmitted Orthoflaviviruses.

DOI: https://doi.org/10.1371/journal.pone.0319207
Front Immunol. 2025 ;16 1475160

Plasma lipidomic alterations during pathogenic SIV infection with and without antiretroviral therapy.

Sindhuja Sivanandham, Ranjit Sivanandham, Cuiling Xu, Jen Symmonds, Paola Sette, Tianyu He, Nicholas Funderburg, Mohamed Abdel-Mohsen, Alan Landay, Cristian Apetrei, Ivona Pandrea.

   Introduction: Lipid profiles change in human immunodeficiency virus (HIV) infection and correlate with inflammation. Lipidomic alterations are impacted by multiple non-HIV-related behavioral risk factors; thus, use of animal models in which these behavioral factors are controlled may inform on the specific lipid changes induced by simian immunodeficiency virus (SIV) infection and/or antiretroviral therapy (ART).
Methods: Using ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy, we assessed and compared (ANOVA) longitudinal lipid changes in naïve and ART-treated SIV-infected pigtailed macaques (PTMs). Key parameters of infection (IL-6, TNFa, D-dimer, CRP and CD4+ T cell counts) were correlated (Spearman) with lipid concentrations at critical time points of infection and treatment.
Results: Sphingomyelins (SM) and lactosylceramides (LCER) increased during acute infection, returning to baseline during chronic infection; Hexosylceramides (HCER) increased throughout infection, being normalized with prolonged ART; Phosphatidylinositols (PI) and lysophosphatidylcholines (LPC) decreased with SIV infection and did not return to normal with ART; Phosphatidylethanolamines (PE), lysophosphatidylethanolamines (LPE) and phosphatidylcholines (PC) were unchanged by SIV infection, yet significantly decreased throughout ART. Specific lipid species (SLS) were also substantially modified by SIV and/or ART in most lipid classes. In conclusion, using a metabolically controlled model, we identified specific lipidomics signatures of SIV infection and/or ART, some of which were similar to people living with HIV (PWH). Many SLS were identical to those involved in development of organ dysfunctions encountered in virally suppressed individuals. Lipid changes also correlated with markers of disease progression, inflammation and coagulation.
Discussion: Our data suggest that lipidomic profile alterations contribute to residual systemic inflammation and comorbidities seen in HIV/SIV infections and therefore may be used as biomarkers of SIV/HIV comorbidities. Further exploration into the benefits of interventions targeting dyslipidemia is needed for the prevention HIV-related comorbidities.

Keywords:  HIV comorbidities; antiretroviral therapy (ART); cardiovascular disease; human immunodeficiency virus (HIV); lipidomics; metabolic disease; simian immunodeficiency virus (SIV)

DOI:  https://doi.org/10.3389/fimmu.2025.1475160
Viruses. 2025 Mar 02. pii: 360. [Epub ahead of print]17(3):

Modulation of Ire1-Xbp1 Defense Pathway in Encephalomyocarditis Virus-Infected HeLa Cells.

Anna Shishova, Yury Ivin, Ekaterina Gladneva, Ksenia Fominykh, Ilya Dyugay, Anatoly Gmyl.

  A key contributor to the pathogenicity of viruses is their interaction with cellular defense mechanisms, including UPR (unfolded protein response) that counteracts the accumulation of misfolded proteins in the endoplasmic reticulum (known as ER stress). One of the UPR branches is mediated by the IRE1 (inositol-requiring enzyme 1) protein, which possesses protein kinase and RNase activities that facilitate the unconventional cytoplasmic splicing of XBP1 mRNA, leading to the upregulation of the XBP1 transcription factor. In this study, we demonstrate that Encephalomyocarditis Virus (Cardiovirus rueckerti) is able to suppress IRE1-dependent XBP1 activation. HeLa cells infection with EMCV resulted in the modulation of phosphorylated IRE1 levels throughout the infection cycle. Viral infection did not result in the accumulation of spliced XBP1 mRNA. Moreover, the addition of a chemical inducer of ER stress (dithiothreitol) to infected cells led to a markedly lower accumulation of spliced XBP1 mRNA as compared to the level of this mRNA in inducer-treated mock-infected cells. Thus, our results demonstrate the ability of picornaviruses to modulate another defensive activity of the host cell.

Keywords:  ER stress; IRE1; UPR; XBP1; encephalomyocarditis virus; unconventional splicing

DOI:  https://doi.org/10.3390/v17030360
J Proteome Res. 2025 Mar 25.

1H NMR Urinary Metabolomics Profiling of Newborns with Congenital Human Cytomegalovirus Infection: Insights into Metabolic Alterations.

Alessia Spadavecchia, Marta Zoccarato, Gaia Tedone, Matteo Biolatti, Valentina Dell'Oste, Agata Leone, Alessandro Cossard, Mattia Sozzi, Ilia Bresesti, Enrico Bertino, Roberto Gobetto, Alessandra Coscia, Angelo Gallo.

  Human cytomegalovirus (HCMV) is the leading cause of congenital infections resulting in severe morbidity and mortality among newborns worldwide. Currently, the most significant prognostic factor of congenital cytomegalovirus (cCMV) infection is the time of maternal infection, with a more severe clinical phenotype if the mother's first outbreak occurs during the first trimester of pregnancy. Nonetheless, the pathogenesis of cCMV infection has still to be completely characterized. In particular, little is known about the metabolic response triggered by HCMV in congenitally infected newborns. As such, urinary metabolic profiling by 1H nuclear magnetic resonance (NMR) might represent a promising tool to be exploited in the context of cCMV. This study aims to investigate the impact of HCMV infection on the urine metabolome in a population of congenitally infected newborns and uninfected controls by 1H NMR spectroscopy combined with multivariate statistical analysis. The 1H NMR spectra of patients (n = 35) and controls (n = 15) allowed the identification of an overall amount of 55 metabolites. Principal Component Analysis (PCA) and clustering correctly assigned 49 out of 50 newborns into the infected and control groups. Partial Least-Squares-Discriminant Analysis (PLS-DA) revealed that newborns with cCMV resulted in having increased betaine, citrate, 3-hydroxybutyrate, 4-hydroxybutyrate, acetoacetate, formate, glycolate, lactate, succinate, and threonine levels in the urine. On the other hand, healthy controls showed increased 4-aminohippurate, creatine, creatinine, fumarate, mannitol, taurine, and dimethylamine levels. These results showed a clear difference in metabolomic fingerprint between newborns with cCMV infection and healthy controls. Thus, metabolomics can be considered a new, promising diagnostic and prognostic tool in the clinical management of cCMV patients.

Keywords:  HCMV; NMR spectroscopy; congenital; cytomegalovirus; infection; metabolomic

DOI:  https://doi.org/10.1021/acs.jproteome.5c00017
Poult Sci. 2025 Mar 16. pii: S0032-5791(25)00293-7. [Epub ahead of print]104(5): 105054

Oxidative stress in the liver of chicken during fowl adenovirus serotype 4 infection.

Jiayu Sun, Xu Cao, Yufeng Li, Kexiang Yu, Yanfang Cong, Qing Pan, Yanbo Yin, Jianlin Wang.

  Hepatitis is a significant pathological manifestation of fowl adenovirus serotype-4 (FAdV-4) infection, which is a crucial factor contributing to the mortality of chickens. The pathophysiology of liver disease is rooted in oxidative stress. The present study aims to investigate the presence of oxidative stress during the liver lesion process in FAdV-4 infection. Specifically, one-day-old specific pathogen-free (SPF) chickens were allocated into three groups, the control group, the infection group, and the quercetin group. The quercetin group received daily oral administration of quercetin. At the age of 12 days, the chickens belonging to both the infection and quercetin groups were subjected to intramuscular injection of FAdV-4 (0.3 mL103TCID50/mL). Samples were collected from each group at 2, 4, and 6 days post-infection (dpi), and sera were collected to measure the levels of ALT and AST. A portion of liver tissue was fixed to examine the histological changes, cell apoptosis, and mitochondrial morphology, while another portion was homogenized and mitochondria were isolated. The levels of MDA, SOD, H2O2, and GSH-Px in the homogenate supernatants of livers and isolated mitochondria were measured, and the viral load in the liver was studied. And Cyt C levels in the mitochondria and cytosolic supernatant were recorded. The results showed that AST and ALT in the serum of chicken in the infection group were significantly higher than those in the control and quercetin group at 6 dpi. Obvious swelling, steatosis, necrosis, and inflammatory cell infiltration were observed in the liver of the infection group. Administered with quercetin can significantly decrease the viral load in the liver at 4 and 6 dpi. H2O2 in the liver, and MDA, H2O2, GSH and SOD levels in mitochondria in the hepatocyte of the infection group were significantly higher than those in the control and quercetin groups. Cyt C in the mitochondria of the hepatocyte of infection and quercetin groups were significantly lower than those in the control group at 2 dpi. Cyt C in the cytoplasm of the liver in chicken in the quercetin group was significantly higher than those in the control and infection groups. It was found that the outer mitochondrial membrane in hepatocytes was fractured in the infection group. The proportion of apoptotic cells in the liver in the infection groups was significantly higher than those in the control and quercetin group at 4 dpi, and that in the control group was significantly lower than in the infection and quercetin group. The results suggested that during liver injury induced by FAdV-4 infection, oxidative damage occurred obviously in the liver and mitochondria, and hepatocyte apoptosis was observed. Quercetin, as an antioxidant, can inhibit virus replication to some extent, and alleviate oxidative damage, liver damage, and the mortality caused by FAdV-4 infection.

Keywords:  Apoptosis; Fowl adenovirus serotype 4; Liver damage; Mitochondria; Oxidative stress

DOI:  https://doi.org/10.1016/j.psj.2025.105054
Metabolites. 2025 Mar 11. pii: 192. [Epub ahead of print]15(3):

Analyses of Saliva Metabolome Reveal Patterns of Metabolites That Differentiate SARS-CoV-2 Infection and COVID-19 Disease Severity.

Violeta Larios-Serrato, Natalia Vázquez-Manjarrez, Osbaldo Resendis-Antonio, Nora Rios-Sarabia, Beatriz Meza, Oliver Fiehn, Javier Torres.

   BACKGROUND: The metabolome of COVID-19 patients has been studied sparsely, with most research focusing on a limited number of plasma metabolites or small cohorts. This is the first study to test saliva metabolites in COVID-19 patients in a comprehensive way, revealing patterns significantly linked to disease and severity, highlighting saliva's potential as a non-invasive tool for pathogenesis or diagnostic studies.
METHODS: We included 30 asymptomatic subjects with no prior COVID-19 infection or vaccination, 102 patients with mild SARS-CoV-2 infection, and 61 hospitalized patients with confirmed SARS-CoV-2 status. Saliva samples were analyzed using hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS/MS) in positive and negative ionization modes.
RESULTS: Significant differences in metabolites were identified in COVID-19 patients, with distinct patterns associated with disease severity. Dipeptides such as Val-Glu and Met-Gln were highly elevated in moderate cases, suggesting specific protease activity related to SARS-CoV-2. Acetylated amino acids like N-acetylserine and N-acetylhistidine increased in severe cases. Bacterial metabolites, including muramic acid and indole-3-carboxaldehyde, were higher in mild-moderate cases, indicating that oral microbiota differs according to disease severity. In severe cases, polyamines and organ-damage-related metabolites, such as N-acetylspermine and 3-methylcytidine, were significantly increased. Interestingly, most metabolites that were reduced in moderate cases were elevated in severe cases.
CONCLUSIONS: Saliva metabolomics offers insightful information that is potentially useful in studying COVID-19 severity and for diagnosis.

Keywords:  COVID-19; metabolome; patient; severity

DOI:  https://doi.org/10.3390/metabo15030192
J Clin Virol. 2025 Mar 17. pii: S1386-6532(25)00022-8. [Epub ahead of print]177 105781

Impact of metformin on HBV replication: No evidence of suppression in vitro.

Cyrus Hawkins, Elizabeth Waddilove, Philippa C Matthews, Marion Delphin.

   BACKGROUND: Outcomes of chronic Hepatitis B (CHB) infection have been increasingly associated with various metabolic syndromes, including metabolic-dysfunction associated steatotic liver disease (MASLD), with a potential for impact on liver disease progression. There is some evidence that metformin, a widely used anti-diabetic drug, may reduce hepatocellular carcinoma (HCC) incidence in people living with Hepatitis B Virus (HBV), but with little to no evidence of impact on the virus itself in vivo. However, previous in vitro studies suggest metformin may have a direct impact on HBV replication, although the mechanism remains unclear.
OBJECTIVES: We aimed to investigate the impact of metformin on HBV replication in vitro.
STUDY DESIGN: Hepatocyte cell lines constitutively expressing HBV (HepAD38) were treated once or thrice with escalating doses of metformin, using lamivudine and water as controls. We monitored cellular cytotoxicity as well as HBV biomarkers (HBeAg, HBsAg, HBV DNA and RNA) throughout the assay.
RESULTS: We did not observe any impact of metformin on HBV replication after a single dose or three repeated treatments.
CONCLUSIONS: In HepAD38 cells, HBV replication is not impacted by metformin treatment. This contrasts with prior in vitro data but is in line with clinical evidence that suggests metformin acts through an influence on liver disease progression rather than a direct antiviral impact on HBV itself.

Keywords:  Hepatitis B Virus; MASLD; Metabolic syndrome; Metformin; Replication; Suppression

DOI:  https://doi.org/10.1016/j.jcv.2025.105781
Trop Med Infect Dis. 2025 Mar 11. pii: 73. [Epub ahead of print]10(3):

Do Statins Affect Viral Infections Encountered by International Travelers?

Chinmay T Jani, Christian Mouchati, Nour Abdallah, Ruchi Jani, Loukas Kakoullis, Lin H Chen.

  Statins are among the most frequently prescribed medications. In addition to their well-established effectiveness in lowering total cholesterol, LDL, and triglycerides, statins have been described to have immunomodulatory and anti-inflammatory properties and have been associated with improved endothelial functions. Given the common use of statins, we sought to evaluate the effect of statins on some viral infections encountered by residents in tropical areas or by international travelers. A literature search was performed in PubMED/MEDLINE focusing on keywords that included statins and the viruses of interest, including SARS-CoV-2, influenza, yellow fever, dengue, Zika, tick-borne encephalitis, hemorrhagic fever viruses, hepatitis A, norovirus, hepatitis B, hepatitis C, measles, and herpesviruses; findings were synthesized for each virus into a summary. The effects of statins on viral infections vary depending on the specific virus. While some studies indicate potential benefits in chronic HBV and HCV infections, evidence regarding SARS-CoV-2 and influenza remains inconclusive due to mixed findings from observational studies and randomized controlled trials. The role of statins in other viral infections is largely unexplored, with preclinical data available for only a few viruses. Given the conflicting evidence, further prospective studies and randomized controlled trials are warranted to elucidate statins' role in viral infections, particularly in modulating inflammation, endothelial dysfunction, and immune responses. Future research should aim to define the optimal patient populations, target viruses, statin types, and treatment durations that may confer benefits in specific viral infections.

Keywords:  COVID-19; Ebola; flavivirus; hepatitis; immunomodulation; influenza; norovirus; statin

DOI:  https://doi.org/10.3390/tropicalmed10030073
Viruses. 2025 Feb 21. pii: 299. [Epub ahead of print]17(3):

Turkey B Cell Transcriptome Profile During Turkey Hemorrhagic Enteritis Virus (THEV) Infection Highlights Upregulated Apoptosis and Breakdown Pathways That May Mediate Immunosuppression.

Abraham Quaye, Brett E Pickett, Joel S Griffitts, Bradford K Berges, Brian D Poole.

  Infection with the turkey hemorrhagic enteritis virus (THEV) can cause hemorrhagic enteritis, which affects young turkeys. This disease is characterized by bloody diarrhea and immunosuppression (IMS), which is attributed to apoptosis of infected B cells. Secondary infections due to IMS exacerbate economic losses. We performed the first transcriptomic analysis of a THEV infection to elucidate the mechanisms mediating THEV-induced IMS. After infecting and sequencing mRNAs of a turkey B-cell line, trimmed reads were mapped to the host turkey genome, and gene expression was quantified with StringTie. Differential gene expression analysis was followed by functional enrichment analyses using gprofiler2 and DAVID from NCBI. RT-qPCR of select genes was performed to validate the RNA-seq data. A total of 2343 and 3295 differentially expressed genes (DEGs) were identified at 12 hpi and 24 hpi, respectively. The DEGs correlated with multiple biological processes including apoptosis, ER unfolded protein response, and cell maintenance. Multiple pro-apoptotic genes, including APAF1, BMF, BAK1, and FAS were upregulated. Genes that play a role in ER stress-induced unfolded protein response including VCP, UFD1, EDEM1, and ATF4 were also upregulated and may contribute to apoptosis. Our data suggest that several biological processes and pathways including apoptosis and ER response to stress are important aspects of the host cell response to THEV infection. It is possible that interplay between multiple processes may mediate apoptosis of infected B-cells, leading to IMS.

Keywords:  B cell; ER stress; RNA sequencing; Turkey hemorrhagic enteritis virus (THEV); adenovirus; apoptosis; immunosuppression

DOI:  https://doi.org/10.3390/v17030299