bims-mevinf Biomed News
on Metabolism in viral infections
Issue of 2025–02–02
fourteen papers selected by
Alexander Ivanov, Engelhardt Institute of Molecular Biology
  1. ASFV infection induces lipid metabolic disturbances and promotes viral replication.
  2. Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung-Derived Cell Lines.
  3. Dengue virus is particularly sensitive to interference with long-chain fatty acid elongation and desaturation.
  4. Infectious Spleen and Kidney Necrosis Virus ORF093R and ORF102R Regulate Glutamate Metabolic Reprogramming to Support Virus Proliferation by Interacting with c-Myc.
  5. Getah virus triggers ROS-mediated autophagy in mouse Leydig cells.
  6. Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections.
  7. Congenital Zika Syndrome: Insights from Integrated Proteomic and Metabolomic Analysis.
  8. Cholesterol metabolism regulator SREBP2 inhibits HBV replication via suppression of HBx nuclear translocation.
  9. Purine but Not Pyrimidine De Novo Nucleotide Biosynthesis Inhibitors Strongly Enhance the Antiviral Effect of Corresponding Nucleobases Against Dengue Virus.
  10. Short-Chain Fatty Acids: Promising Therapeutic Targets for Respiratory Syncytial Virus Infection.
  11. Metabolomic Profiling Reveals Potential Biomarkers and Prominent Features in HIV/AIDS Patients Co-Infected with SARS-CoV-2.
  12. Baculoviruses manipulate host lipid metabolism via adipokinetic hormone signaling to induce climbing behavior.
  13. The role of lipids and lipids lowering drugs in human papillomavirus (HPV) and HPV-associated cancers.
  14. HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients' clinical stage.
  1. Front Microbiol. 2024 ;15 1532678
    ASFV infection induces lipid metabolic disturbances and promotes viral replication.
    Xuefei Chu, Shengqiang Ge, Yingchao Li, Qin Zhang, Xinyu Cui, Yuanyuan Zuo, Ruihong Li, Hongtao Sun, Lei Yin, Zhenzhong Wang, Jinming Li, Yihong Xiao, Zhiliang Wang.
       Introduction: African swine fever is a highly transmissible and lethal infectious disease caused by the African swine fever virus (ASFV), which has considerably impacted the global swine industry. Lipid metabolism plays a vital role in sustaining lipid and energy homeostasis within cells and influences the viral life cycle.
    Methods and results: In this study, we found that ASFV infection disrupts lipid metabolism in the host. Transcriptomic analysis of cells infected with ASFV revealed that the levels of lipid metabolism significantly changed as the duration of the infection progressed. The intracellular cholesterol levels of the host exhibited a pattern similar to the viral growth curve during the course of infection. Notably, increased cholesterol levels promoted ASFV replication in host cells, whereas inhibition of the cholesterol biosynthesis pathway markedly reduced intracellular ASFV replication.
    Discussion: The findings of this study showed that ASFV led to lipid metabolism disturbances to facilitate its replication, which is useful for revealing the mechanism underlying ASFV infection.
    Keywords:  African swine fever virus; cholesterol; lipid metabolism; lipid synthesis; transcriptomic analysis
    DOI:  https://doi.org/10.3389/fmicb.2024.1532678
  2. Viruses. 2025 Jan 16. pii: 120. [Epub ahead of print]17(1):
    Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung-Derived Cell Lines.
    David M Renner, Nicholas A Parenti, Nicole Bracci, Susan R Weiss.
      The betacoronavirus genus contains five of the seven human coronaviruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus-HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus), and MERS-CoV (merbecovirus)-, to study betacoronavirus interactions with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation. We demonstrate that MERS-CoV, HCoV-OC43, and SARS-CoV-2 all activate PERK and induce responses downstream of p-eIF2α, while only SARS-CoV-2 induces detectable p-eIF2α during infection. Using a small molecule inhibitor of eIF2α dephosphorylation, we provide evidence that MERS-CoV and HCoV-OC43 maximize viral replication through p-eIF2α dephosphorylation. Interestingly, genetic ablation of growth arrest and DNA damage-inducible protein (GADD34) expression, an inducible protein phosphatase 1 (PP1)-interacting partner targeting eIF2α for dephosphorylation, did not significantly alter HCoV-OC43 or SARS-CoV-2 replication, while siRNA knockdown of the constitutive PP1 partner, constitutive repressor of eIF2α phosphorylation (CReP), dramatically reduced HCoV-OC43 replication. Combining GADD34 knockout with CReP knockdown had the maximum impact on HCoV-OC43 replication, while SARS-CoV-2 replication was unaffected. Overall, we conclude that eIF2α dephosphorylation is critical for efficient protein production and replication during MERS-CoV and HCoV-OC43 infection. SARS-CoV-2, however, appears to be insensitive to p-eIF2α and, during infection, may even downregulate dephosphorylation to limit host translation.
    Keywords:  HCoV-OC43; MERS-CoV; PERK pathway; PKR pathway; SARS-CoV-2; coronavirus; integrated stress response
    DOI:  https://doi.org/10.3390/v17010120
  3. J Biol Chem. 2025 Jan 23. pii: S0021-9258(25)00069-9. [Epub ahead of print] 108222
    Dengue virus is particularly sensitive to interference with long-chain fatty acid elongation and desaturation.
    Julia Hehner, Lisa Ludenia, Laura Bierau, Anja Schöbel, Martin Schauflinger, Yvonne F Grande, Dominik Schwudke, Eva Herker.
      Orthoflaviviruses are emerging arthropod-borne pathogens whose replication cycle is tightly linked to host lipid metabolism. Previous lipidomic studies demonstrated that infection with the closely related hepatitis C virus (HCV) changes the fatty acid (FA) profile of several lipid classes. Lipids in HCV-infected cells had more very long-chain and desaturated FAs and viral replication relied on functional FA elongation and desaturation. Here, we systematically analyzed the role of FA elongases and desaturases in infection models of the most prevalent pathogenic orthoflaviviruses, dengue (DENV), Zika (ZIKV), West Nile (WNV), yellow fever (YFV), and tick-borne encephalitis virus (TBEV). Knockdown of desaturases and elongases in Huh7 cells only marginally affected ZIKV, WNV, YFV, and TBEV replication, while DENV titers were strongly reduced. This was most prominent for enzymes involved in very long-chain fatty acid synthesis. In detail, knockdown of the FA elongase ELOVL4, which catalyzes ultra long-chain FA synthesis, significantly reduced DENV titers, decreased the formation of replication intermediates, and lowered viral protein levels in DENV infected hepatoma cells, suggesting a function of ELOVL4 in DENV RNA replication. In contrast, the activity of FA desaturase FADS2, rate-limiting in poly-unsaturated FA biosynthesis, is not involved in viral RNA replication or translation, but is essentially required for formation of infectious DENV particles. Further, in immunocompetent immortalized microglial cells, FADS2 deletion additionally limits viral replication through increased expression of interferon-stimulated genes in response DENV infection. Taken together, enzymes involved in very long-chain FA synthesis are critical for different steps of DENV replication.
    Keywords:  fatty acid metabolism; flavivirus; host-pathogen interaction; lipid; polyunsaturated fatty acid (PUFA); virus
    DOI:  https://doi.org/10.1016/j.jbc.2025.108222
  4. Int J Mol Sci. 2025 Jan 16. pii: 718. [Epub ahead of print]26(2):
    Infectious Spleen and Kidney Necrosis Virus ORF093R and ORF102R Regulate Glutamate Metabolic Reprogramming to Support Virus Proliferation by Interacting with c-Myc.
    Yinjie Niu, Caimei Ye, Qiang Lin, Hongru Liang, Xia Luo, Baofu Ma, Ningqiu Li, Xiaozhe Fu.
      Glutamine metabolism is essential for infectious spleen and kidney necrosis virus (ISKNV) replication. Glutaminase 1 (GLS1), the key enzyme of the glutamine metabolism, and c-Myc positively regulate ISKNV infection, while c-Myc is closely correlated with GLS1. However, the regulatory mechanism among ISKNV, c-Myc and glutamine metabolism remains unclear. Here, we indicated that c-Myc increased glutamine uptake by increasing the GLS1, glutamate dehydrogenase (GDH) and isocitrate dehydrogenase (IDH2) expression of glutamine metabolism. ISKNV ORF102R, ORF093R and ORF118L co-located with c-Myc in CPB cells. Co-IP results showed that ISKNV ORF102R and ORF093R interacted with c-Myc, while ORF118L did not interact with c-Myc. The expression levels of c-Myc, GLS1 and IDH2 were increased in ISKNV ORF093R expression cells, and the mRNA and protein levels of GLS1 were upregulated in ISKNV 102R-expressing cells. These results indicated that ISKNV reconstructed glutamine metabolism to satisfy the energy and macromolecule requirements for virus proliferation by ORF093R and ORF102R interacting with c-Myc, which provides the foundation for innovative antiviral strategies.
    Keywords:  ISKNV; c-Myc; glutamine metabolism
    DOI:  https://doi.org/10.3390/ijms26020718
  5. Front Microbiol. 2024 ;15 1519694
    Getah virus triggers ROS-mediated autophagy in mouse Leydig cells.
    Fengqin Li, Lishuang Deng, Tong Xu, Lei Xu, Zhiwen Xu, Siyuan Lai, Yanru Ai, Yanqun Wang, Guangwen Yan, Ling Zhu.
       Introduction: Getah virus (GETV) is a zoonotic virus transmitted via a mosquito-vertebrate cycle. While previous studies have explored the epidemiology and pathogenicity of GETV in various species, its molecular mechanisms remain largely unexplored.
    Methods: This study investigated the impact of GETV infection and associated molecular mechanisms on reactive oxygen species (ROS) and autophagy levels in mouse Leydig cells both in vivo and in vitro. The male mice and TM3 cells were treatment with N-acetylcysteine (NAC) to reduce cellular ROS levels. Rapamycin (Rapa) and 3-Methyladenine (3- MA) were used to change autophagy in both infected and uninfected TM3 cells.
    Results and Discussion: The findings revealed that GETV infection in mouse testes speciffcally targeted Leydig cells and induced oxidative stress while enhancing autophagy in testicular tissue. Using TM3 cells as an in vitro model, the study confirmed GETV replication in this cell line, triggering increased ROS and autophagy levels. Treatment with N-acetylcysteine (NAC) to reduce cellular ROS levels markedly reduced autophagy in testicular tissue and TM3 cells infected with GETV. Interestingly, the use of rapamycin (Rapa) and 3-Methyladenine (3- MA) led to autophagy change in both infected and uninfected TM3 cells, with no signiffcant alterations in cellular ROS levels. These results indicate that GETV infection elevates ROS levels, subsequently inducing autophagy in mouse Leydig cells. We also found that autophagy plays an important role in GETV replication. When autophagy levels were reduced using NAC and 3-MA, a corresponding decrease in TCID50 was observed. Conversely, upregulation of autophagy using Rapa resulted in an increase in TCID50 of GETV. Therefore, we speculate that GETV may exploit the autophagy pathway to facilitate its replication. These ffndings illuminate the interplay between GETV and host cells, providing valuable insights for therapeutic strategies targeting autophagy in GETV infections.
    Keywords:  Getah virus; Leydig cells; ROS; autophagy; mouse
    DOI:  https://doi.org/10.3389/fmicb.2024.1519694
  6. Viruses. 2024 Dec 25. pii: 11. [Epub ahead of print]17(1):
    Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections.
    Jennifer Molle, Sarah Duponchel, Jennifer Rieusset, Michel Ovize, Alexander V Ivanov, Fabien Zoulim, Birke Bartosch.
      Cyclophilin (Cyp) inhibitors are of clinical interest in respect to their antiviral activities in the context of many viral infections including chronic hepatitis B and C. Cyps are a group of enzymes with peptidyl-prolyl isomerase activity (PPIase), known to be required for replication of diverse viruses including hepatitis B and C viruses (HBV and HCV). Amongst the Cyp family, the molecular mechanisms underlying the antiviral effects of CypA have been investigated in detail, but potential roles of other Cyps are less well studied in the context of viral hepatitis. Furthermore, most studies investigating the role of Cyps in viral hepatitis did not investigate the potential therapeutic effects of their inhibition in already-established infections but have rather been performed in the context of neo-infections. Here, we investigated the effects of genetically silencing Cyps on persistent HCV and HBV infections. We confirm antiviral effects of CypA and CypD knock down and demonstrate novel roles for CypG and CypH in HCV replication. We show, furthermore, that CypA silencing has a modest but reproducible impact on persistent HBV infections in cultured human hepatocytes.
    Keywords:  anti-viral treatment; cyclophilin; hepatitis virus; liver
    DOI:  https://doi.org/10.3390/v17010011
  7. Biomolecules. 2024 Dec 30. pii: 32. [Epub ahead of print]15(1):
    Congenital Zika Syndrome: Insights from Integrated Proteomic and Metabolomic Analysis.
    Leticia Gomes-de-Pontes, Lucila Akune Barreiros, Lillian Nunes Gomes, Ranieri Coelho Salgado, Sarah Maria da Silva Napoleão, Paulo V Soeiro-Pereira, Saulo Duarte Passos, Antonio Condino-Neto.
      Background: In this study, we investigated the role of extracellular vesicles (EVs) in the pathogenesis of Congenital Zika Syndrome (CZS). Previous studies have highlighted the role of EVs in intercellular communication and the modulation of biological processes during viral infections, motivating our in-depth analysis. Our objective was to identify specific molecular signatures in the EVs of patients with CZS, focusing on their potential as biomarkers and on cellular pathways affected by the infection. Methods: We conducted advanced proteomic and metabolomic analyses using mass spectrometry for protein and metabolite identification. EVs were isolated from CZS patient samples and control groups using Izon qEV size-exclusion chromatography columns. Results: The analyzed EVs presented distinct molecular profiles in patients with CZS. Proteomic analysis revealed significant alterations in specific proteins, suggesting involvement in the PI3K-AKT-mTOR pathway, while metabolomics highlighted metabolites related to critical processes in Zika virus pathogenesis. These findings suggest a key role for the PI3K-AKT-mTOR pathway in regulating cellular processes during infection and indicate the involvement of EVs in intercellular communication. Additionally, the results identified potential biomarkers capable of aiding early diagnosis and assessing disease progression. Conclusions: This study demonstrates that EVs play a crucial role in intercellular communication during Zika virus infection. The identification of specific alterations in the PI3K-AKT-mTOR pathway highlights a possible therapeutic target, providing new opportunities for the development of more effective treatment strategies for CZS. Our findings significantly advance the understanding of CZS and underscore the need for further investigations using advanced techniques to validate and explore these potential molecular targets.
    Keywords:  Zika infection; extracellular; metabolome; proteome; vesicles
    DOI:  https://doi.org/10.3390/biom15010032
  8. Front Immunol. 2024 ;15 1519639
    Cholesterol metabolism regulator SREBP2 inhibits HBV replication via suppression of HBx nuclear translocation.
    Fan Yang, Feng Hu, Hongxiao Song, Tie Li, Fengchao Xu, Jing Xu, Le Wang, Fei Wang, Yujia Zhu, Mian Huang, Yanli Gao, Min Rao, Haichun Ma, Guangyun Tan.
      The intricate link between cholesterol metabolism and host immune responses is well recognized, but the specific mechanisms by which cholesterol biosynthesis influences hepatitis B virus (HBV) replication remain unclear. In this study, we show that SREBP2, a key regulator of cholesterol metabolism, inhibits HBV replication by interacting directly with the HBx protein, thereby preventing its nuclear translocation. We also found that inhibiting the ER-to-Golgi transport of the SCAP-SREBP2 complex or blocking SREBP2 maturation significantly enhances HBV suppression. Notably, we demonstrate that the C-terminal domain (CTD) of SREBP2, rather than its N-terminal domain (NTD), mediates this inhibition by interacting with HBx and promoting its extracellular secretion, thus reducing nuclear HBx accumulation. These findings reveal a novel regulatory pathway that links cholesterol metabolism to HBV replication via SREBP2-mediated control of HBx localization. This insight provides a potential basis for new therapeutic strategies against HBV infection, addressing an important global health issue.
    Keywords:  HBV - hepatitis B virus; HBV replication; HBx; SREBP2; cholesterol metabolism
    DOI:  https://doi.org/10.3389/fimmu.2024.1519639
  9. Molecules. 2025 Jan 07. pii: 210. [Epub ahead of print]30(2):
    Purine but Not Pyrimidine De Novo Nucleotide Biosynthesis Inhibitors Strongly Enhance the Antiviral Effect of Corresponding Nucleobases Against Dengue Virus.
    Laurent F Bonnac, Christine D Dreis, Madhu Rai, Robert J Geraghty.
      Every year, dengue virus affects hundreds of millions of individuals worldwide. To date, there is no specific medication to treat dengue virus infections. Nucleobases, the base of a nucleoside without ribose, are understudied as potential treatments for viral infections. Antiviral nucleobases are converted in infected cells to their corresponding nucleoside triphosphate active form. Importantly, the conversion of nucleobases to their active nucleotide form and their antiviral effect can be enhanced when combined with de novo nucleotide biosynthesis inhibitors. In this work, we evaluated seven purine and pyrimidine nucleobases alone or combined with six purine or pyrimidine de novo nucleotide biosynthesis inhibitors, including novel prodrugs. Our study revealed that while a strong potentiation of purine nucleobases by purine de novo nucleotide biosynthesis inhibitors was observed, the pyrimidine nucleobases were not potentiated by pyrimidine de novo nucleotide biosynthesis inhibitors, possibly highlighting a significant difference between the modulation of purine versus pyrimidine de novo pathways and their impact on nucleobase potentiation. Most significant antiviral effects and potentiation were observed for Favipiravir, T-1105, and ribavirin nucleobases combined with purine nucleotide de novo synthesis inhibitors. These results are significant because drug combinations may solve the limited efficacy observed for some antiviral nucleobase drugs such as Favipiravir.
    Keywords:  broad-spectrum antivirals; drug combination; flaviviruses; nucleobases
    DOI:  https://doi.org/10.3390/molecules30020210
  10. Clin Rev Allergy Immunol. 2025 Jan 28. 68(1): 8
    Short-Chain Fatty Acids: Promising Therapeutic Targets for Respiratory Syncytial Virus Infection.
    Mingxin Liang, Qinqin Dong, Weiyi Wu, Juan Fan.
      The intestinal microbiota is a complex community of organisms present in the human gastrointestinal tract, some of which can produce short-chain fatty acids (SCFAs) through the fermentation of dietary fiber. SCFAs play a major role in mediating the intestinal microbiota's regulation of host immunity and intestinal homeostasis. Respiratory syncytial virus (RSV) can cause an imbalance between anti-inflammatory and proinflammatory responses in the host. In addition, changes in SCFA levels and the structure of the intestinal microbiota have been observed after RSV infection. Therefore, there may be a link between SCFAs and RSV infection, and SCFAs are expected to be therapeutic targets for RSV infection.
    Keywords:  Immunity; Intestinal microbiome; Probiotics; Respiratory syncytial virus; Short-chain fatty acids
    DOI:  https://doi.org/10.1007/s12016-024-09018-x
  11. Microorganisms. 2025 Jan 13. pii: 144. [Epub ahead of print]13(1):
    Metabolomic Profiling Reveals Potential Biomarkers and Prominent Features in HIV/AIDS Patients Co-Infected with SARS-CoV-2.
    Xuan Yan, Xinyu Zhang, Wei Song, Tangkai Qi, Zhenyan Wang, Yang Tang, Jianjun Sun, Shuibao Xu, Junyang Yang, Jiangrong Wang, Jun Chen, Renfang Zhang, Li Liu, Yinzhong Shen.
      The underlying mechanisms and diagnostic biomarkers for the progress of COVID-19 in HIV patients have not been fully elucidated. In this study, the aim is to analyze the metabolomic profiles of HIV/AIDS patients co-infected with SARS-CoV-2 and to identify biomarkers indicative of co-infection. In this study, we conducted a retrospective cohort analysis of peripheral blood samples collected from 30 HIV/AIDS patients co-infected with SARS-CoV-2 (pc group) and 30 patients without SARS-CoV-2 (nc group). In this study, through non-targeted metabolomics and lipidomics analysis, 77 differential metabolites were identified in the plasma of patients co-infected with HIV and SARS-CoV-2 compared to the nc group, with vitamin K1 emerging as a significant feature. Moreover, the plasma of the pc group showed disturbances in lipid metabolism, with elevated triglycerides (TG) and phosphatidylcholine (PC) and decreased phosphatidylglycerol (PG) compared to the control group. Vitamin K1 may be a biomarker for SARS-CoV-2 in HIV/AIDS patients, and changes in the levels of TG, PC, and PG molecules appear to be the main features following HIV co-infection with COVID-19. The emphasis in our study is on the power of using comprehensive metabolomics (lipidomics) approaches to identify metabolic biomarkers and potential mechanisms of COVID-19 in HIV/AIDS patients.
    Keywords:  HIV; SARS-CoV-2; lipid metabolism; metabolic biomarkers; untargeted metabolomics
    DOI:  https://doi.org/10.3390/microorganisms13010144
  12. PLoS Pathog. 2025 Jan 31. 21(1): e1012932
    Baculoviruses manipulate host lipid metabolism via adipokinetic hormone signaling to induce climbing behavior.
    Lin Zhu, Yuqing Xie, Chenxi Liu, Jie Cheng, Zhongjian Shen, Xiaoming Liu, Limei Cai, Xinyuan Ning, Songdou Zhang, Zhen Li, Qiuying Huang, Xiaoxia Liu.
      Baculoviruses can induce climbing behavior in caterpillar hosts, which provides an excellent model for studying parasite manipulation of host behavior. Herein, we found that Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) promoted lipid metabolism of infected H. armigera larvae, and changes in lipid metabolism can affect climbing behavior. Therefore, understanding the molecular mechanisms between lipid metabolism and climbing behavior is particularly important. In this study, we found adipokinetic hormone 1 (HaAKH1), adipokinetic hormone 2 (HaAKH2) and their receptor HaAKHR were essential for promoting lipid metabolism and climbing behavior in response to HearNPV infection. Both molecular docking result and Ca2+ imaging showed that both HaAKH1 and HaAKH2 could interact with HaAKHR. Knockdown of HaAKH1, HaAKH2 and HaAKHR resulted in not only the accumulation of triacylglycerol (TAG), but also the reduction of the replication of HearNPV and the crawling ability of infected H. armigera larvae, resulting in a decrease in the final death height of the infected larvae. We further validated this conclusion by injecting active peptides of HaAKH1 and HaAKH2 to infected larvae. In addition, we investigated the downstream of HaAKH signaling and found that hormone-sensitive lipase (HaHSL) changed with changes in HaAKH signaling and HaHSL played the same role as HaAKH signaling. These findings not only revealed the mechanism by which parasites manipulated host lipid metabolism, but more significantly, explored the relationship between lipid metabolism and behavioral changes of hosts manipulated by parasites, broadening our understanding of the phenomenon of parasites manipulating host behavioral changes.
    DOI:  https://doi.org/10.1371/journal.ppat.1012932
  13. Infect Agent Cancer. 2025 Jan 28. 20(1): 4
    The role of lipids and lipids lowering drugs in human papillomavirus (HPV) and HPV-associated cancers.
    Ehsan Shabani, Aida Hasanzadi, Omer Qutaiba B Allela, Radhwan Abdul Kareem, Riyad E Abed, Ali M Ali Al-Nuaimi, Zainab H Athab, Shiva Khodarahmi.
      Both women and men are now confronted with the grave threat of cancers caused by the human papillomavirus (HPV). It is estimated that 80% of women may encounter HPV over their lives. In the preponderance of cases involving anal, head and neck, oral, oropharyngeal, penile, vaginal, vulvar, and cervical malignancies, high-risk HPV (HR-HPV) is the causative agent. In 2019, HPV is believed to have been the cause of 620,000 new cases of cancer in women and 70,000 new cases of cancer in men worldwide. The bulk of the 530,000 cervical cancer cases (~ 270,000 fatalities) caused by HPV infection (86% of cases, 88% of deaths) happen in poor nations each year. Lipid metabolism is crucial in HPV infection and cancer development related to HPV. One of the most noticeable metabolic abnormalities in cancer is lipid metabolism reprogramming, in which cancer cells dysregulate lipid metabolism to obtain sufficient energy, building blocks for cell membranes, and signaling molecules necessary for invasion, metastasis, proliferation, and survival. Moreover, HPV proteins' stimulation of lipid production in infected cells will probably have a significant effect on oncogenesis. In addition, lipids are critical in producing cellular energy, the epithelial-mesenchymal transition (EMT) process, and therapy resistance of HPV-related cancers (HRCs). Therefore, lipids are essential in HPV infection and HRC development and may also be an important target for new approaches associated with treatments during HPV infection or cancer development. This review study looked at the role of lipids and lipid-lowering drugs in HPV and related cancers.
    Keywords:  Cholesterol; HPV-related cancers; Human papillomavirus (HPV); Lipid metabolism; Lipid-lowering drugs
    DOI:  https://doi.org/10.1186/s13027-025-00635-5
  14. Hepatol Commun. 2025 Feb 01. pii: e0625. [Epub ahead of print]9(2):
    HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients' clinical stage.
    Lucile Dumolard, Theophile Gerster, Florent Chuffart, Thomas Decaens, Marie-Noelle Hilleret, Sylvie Larrat, Philippe Saas, Evelyne Jouvin-Marche, David Durantel, Patrice N Marche, Zuzana Macek Jilkova, Caroline Aspord.
       BACKGROUND: Hepatitis B is a liver infection caused by HBV. Infected individuals who fail to control the viral infection develop chronic hepatitis B and are at risk of developing life-threatening liver diseases, such as cirrhosis or liver cancer. Dendritic cells (DCs) play important roles in the immune response against HBV but are functionally impaired in patients with chronic hepatitis B. The underlying mechanisms involved in HBV-induced DC dysfunctions remain to be elucidated.
    METHODS: We explored DC modulations by HBV and HBsAg by exposing blood-derived cDC1s, cDC2s, and plasmacytoid DCs from healthy donors to HBV or HBsAg and stimulating them with toll-like receptor ligand. Their phenotypic and functional features, as well as their metabolic profile, were analyzed through multiparametric flow cytometry and multiplex assays and further explored on patients' samples.
    RESULTS: We found that HBV deeply reshaped the DC secretome in response to toll-like receptor ligand. Strikingly, we observed that HBV-exposed DCs secrete high levels of CX3CL1 (fractalkine), a chemokine responsible for attracting antiviral effectors to the site of infection. HBsAg exposure favored DC activation while drastically altering TRAIL expression in response to toll-like receptor ligand and increasing the secretion of cytokines/chemokines involved in immune tolerance. HBsAg further dampened the metabolism of DC subsets while driving metabolic switches. Notably, the relevance of the CX3CL1/CX3CR1 axis, TGF-β, and metabolic disturbances was demonstrated within intrahepatic DC subsets in patients according to disease stage.
    CONCLUSIONS: Our work brings new insights into the immunomodulation induced by HBV on DCs, which contribute to impaired antiviral responses and progression toward chronicity.
    DOI:  https://doi.org/10.1097/HC9.0000000000000625
This page is being maintained by Thomas Krichel. It was last updated on 2025‒08‒03 at 9:49.