Virology Journal最新文献

{"title":"Identification and profiling of novel metagenome assembled uncultivated virus genomes from human gut.","authors":"Kanchan Bhardwaj, Niharika, Anjali Garg, Aakriti Jain, Manish Kumar, Manish Datt, Vijay Singh, Sudhanshu Vrati","doi":"10.1186/s12985-025-02739-1","DOIUrl":"10.1186/s12985-025-02739-1","url":null,"abstract":"<p><p>Metagenomics has revealed an unprecedented viral diversity in human gut although, most of the sequence data remains uncharacterized. In this study, we mined a collection of 1090 metagenome assembled \"high quality\" viral genomes (> 90% completeness, as determined by CheckV) derived from human fecal samples. Sequence analysis revealed eight new species spanning seven genera within the class, Caudoviricetes and nineteen new species from fourteen genera within the ssDNA virus family, Microviridae. Additionally, four \"high quality\" genomes were not found in any of the four major viral databases, NCBI viral RefSeq, IMG-VR, Gut Phage Database (GPD) and Gut Virome Database (GVD). Further, annotation and KEGG pathway analysis of the \"high-quality\" genomes identified seven core genes (antB, dnaB, DNMT1, DUT, xlyAB, xtmB and xtmA) associated with metabolism and fundamental viral processes. Moreover, genes for virulence, host-takeover, drug resistance, tRNA, tmRNA and CRISPR elements were also detected. Host prediction analysis suggest bacterial hosts for approximately 40% of the genomes. Overall, this study reports the discovery of novel viral genomes and provides a comprehensive genome profiling of human gut viruses in a subpopulation from India. These findings serve as a foundation for future biological investigations to elucidate the role of these viruses in host physiology.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"254"},"PeriodicalIF":4.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclosporin A alleviates influenza A (H1N1) virus-induced chronic pulmonary inflammation through decreasing IFN-γ-producing T lymphocytes.","authors":"Wenbin Ding, Xin Zhao, Zhengyang Lin, Mengxi Luo, Nanshan Zhong, Kefang Lai, Zheng Deng","doi":"10.1186/s12985-025-02887-4","DOIUrl":"10.1186/s12985-025-02887-4","url":null,"abstract":"<p><p>Influenza causes 3-5 million severe cases globally each year, with severe viral pneumonia often requiring hospitalization for over four weeks. While the inflammatory response to influenza infection helps control viral replication, excessive inflammation is a key driver of disease severity and mortality. Excessive pulmonary lymphocytes, particularly IFN-γ-producing T lymphocytes, contribute significantly to pulmonary inflammation at the late-stage of H1N1 viral infection. Cyclosporin A, a potent T-cell inhibitor, mitigates influenza A virus-induced pulmonary inflammation in mice. However, the therapeutic role of lymphocyte suppression in cyclosporin A-mediated attenuation of H1N1 virus-induced chronic pulmonary inflammation remains unclear. Here, we demonstrated that the viral titer was 0 in all the homogenized lung tissues of mice on Day-21 post a sublethal H1N1 viral infection. H1N1 viral infection caused worsened general condition and pulmonary inflammation with the infiltration of lymphocytes and neutrophils on Day-21 post-infection. The bronchoalveolar lavage fluid of H1N1 virus-infected mice showed a 16-fold higher lymphocyte count compared to neutrophils. H1N1 viral infection significantly elevated both IFN-γ-producing T lymphocyte populations and IFN-γ levels in mouse lungs. H1N1 viral infection additionally expanded IFN-γ-producing T lymphocyte populations in both spleen and peripheral blood. Cyclosporin A treatment significantly mitigated H1N1 viral infection-induced worsened general condition, pulmonary lymphocytic inflammation, increases of pulmonary IFN-γ concentrations and IFN-γ-producing T lymphocytes in the lung, spleen and blood of mice on Day-21 post-infection. Together, lymphocytes may contribute significantly to H1N1 virus-induced chronic pulmonary inflammation. Cyclosporin A may alleviate H1N1 virus-induced chronic pulmonary inflammation through decreasing IFN-γ-producing T lymphocytes.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"255"},"PeriodicalIF":4.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humoral and cellular immune response to a single dose of a novel bivalent recombinant adenovirus-vector vaccine against West Nile virus and chikungunya virus in mice.","authors":"Shu Chang, Guo Xiaojuan, Han Xiaotian, Li Mengzhe, Zhai Chengcheng, Bing Jialuo, Jin Liye, Jiang Yujie, Li Jia, Wang Tangqi, Qi Zhenyong, Zhai Desheng, Deng Yao, Lu Zhuozhuang, Tan Wenjie","doi":"10.1186/s12985-025-02878-5","DOIUrl":"10.1186/s12985-025-02878-5","url":null,"abstract":"<p><strong>Background: </strong>West Nile virus (WNV) and chikungunya virus (CHIKV) are zoonotic pathogens transmitted by mosquitoes, which cause significant morbidity and mortality globally. Currently, no human vaccine is available against both WNV and CHIKV.</p><p><strong>Methods: </strong>In this study, we developed a novel bivalent recombinant human adenovirus type 5 (Ad5)-based vaccine, designated Ad5-WNV-CHIKV, which encodes WNV prM-E and CHIKV E3-E2-6 K-E1 antigens. The expression of the target antigens for WNV and CHIKV was validated through western blotting and an immunofluorescence assay. We subsequently assessed the humoral and cellular immune response in C57BL/6 mice following intramuscular administration of a single dose of Ad5-WNV-CHIKV.</p><p><strong>Results: </strong>Both low-dose (2 × 10⁸ viral particles [vp] per mouse) and high-dose (1 × 10⁹ vp per mouse) administration of Ad5-WNV-CHIKV elicited robust immune responses against the viral targets, with specific immunoglobulin G production against WNV-E, CHIKV E1, and CHIKV E2 proteins, and generation of neutralizing antibodies against WNV and CHIKV, in a dose-dependent manner. Moreover, the vaccine induced strong cellular immunity, characterized by multifunctional antigen-reactive CD4⁺ and CD8⁺ T-cell populations, as determined by ELISpot and intracellular cytokine staining assays.</p><p><strong>Conclusion: </strong>A single dose of the bivalent Ad5-WNV-CHIKV vaccine induced strong neutralizing antibody and cellular immune responses against both WNV and CHIKV in mice. These findings provide a foundation for the development of vaccines targeting WNV and CHIKV. A single dose of vaccine could potentially prevent both diseases.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"256"},"PeriodicalIF":4.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiles and kinetics of PgRNA and clinical characteristics in pregnant, postpartum, and non-pregnant women with chronic HBV infection.","authors":"Genju Wang, Yandan Wu, Ziyue Zhang, Qiuchen Wu, Juan Tang, Ying Ji, Yan Wang, Guanlun Zhou, Minmin Yu","doi":"10.1186/s12985-025-02871-y","DOIUrl":"10.1186/s12985-025-02871-y","url":null,"abstract":"<p><strong>Background: </strong>Pregenomic RNA (pgRNA) has been utilized as an early predictive marker for antiviral therapy, an indicator for the emergence of drug resistance in hepatitis B virus (HBV), or a marker for safe discontinuation of nucleoside analog therapy. However, its role during pregnancy has rarely been reported. We aimed to evaluate the pgRNA profiles and its dynamic changes among pregnant, postpartum, and non-pregnant women with chronic HBV infection (CHB).</p><p><strong>Methods: </strong>We conducted a study involving 479 women with CHB, including 235 during pregnancy, 90 postpartum, and 154 non-pregnant women of childbearing age. pgRNA was detected using the HBV-SAT method. Additionally, we followed up 39 women in mid-pregnancy, 21 in late pregnancy, 20 within 0-3 months postpartum, and 20 non-pregnant women of childbearing age with different treatment regimens for two times.</p><p><strong>Results: </strong>Significant differences were observed in clinical indicators such as HBV DNA, ALT, AST, and pgRNA among CHB women during pregnancy, postpartum, and non-pregnant periods. Pregnant and postpartum women with positive pgRNA had higher levels of DNA, HBeAg, HBsAg, and ALT. Moreover, the detection rates of pgRNA, DNA, and HBeAg varied significantly across the three stages and different treatment regimens in CHB women. pgRNA was highly correlated with HBeAg, and a moderate correlation was found between pgRNA and HBV DNA levels. This study also revealed the patterns of viral activity changes during pregnancy and postpartum, and the first three months postpartum represent a critical period for viral activity changes. This unique immune adjustment phase may offer new opportunities for the treatment of hepatitis B.</p><p><strong>Conclusion: </strong>CHB women have different pgRNA and clinical characteristics during pregnancy, postpartum, and the non-pregnant childbearing period.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"250"},"PeriodicalIF":4.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular DNA, hyaluronic acid, HIF pathways, and LncRNAs as predictive biomarkers of severe COVID-19.","authors":"Evgen Dubrovskyi, Tetiana Drevytska, Alla Portnychenko, Victor Dosenko, Iryna Halabitska, Pavlo Petakh, Denis E Kainov, Oleksandr Kamyshnyi","doi":"10.1186/s12985-025-02886-5","DOIUrl":"10.1186/s12985-025-02886-5","url":null,"abstract":"<p><p>The clinical course of COVID-19 ranges from mild symptoms to severe complications, and common laboratory markers such as D-dimer, ferritin, interleukin-6 (IL-6), and C-reactive protein (CRP) often do not accurately predict which patients will develop severe disease. In this study, we reviewed current literature and analyzed additional data to assess emerging biomarkers that may help identify high-risk cases earlier. These include circulating cell-free DNA (cfDNA) produced during neutrophil extracellular trap formation (NETosis), hyaluronic acid (HA), hypoxia-inducible factor (HIF) isoforms, and related long non-coding RNAs such as HAS2-AS1 and HIF1-AS1. Increased levels of cfDNA/NETs, HA, and elevated expression of HIF isoforms and their lncRNAs are closely associated with key features of severe COVID-19, including immune-related blood clotting, low oxygen levels, vascular damage, and chronic inflammation. These biomarkers show promise for use in risk assessment tools that could support earlier clinical decisions and improve outcomes in patients with COVID-19.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"252"},"PeriodicalIF":4.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic characteristics in orthoflaviviral infections: unveiling pathogenic mechanisms and therapeutic targets.","authors":"Zhiwei Su, Ningze Sun, Xiaoyan Zheng","doi":"10.1186/s12985-025-02888-3","DOIUrl":"10.1186/s12985-025-02888-3","url":null,"abstract":"<p><p>Infections caused by mosquito-borne viruses such as Dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) have become a global public health issue. However, due to the unclear pathogenic mechanisms, there are currently no specific treatments available for patients infected with these orthoflaviviruses in clinical practice. Metabolomics provides distinct advantages for characterizing infection features and deciphering disease pathogenesis. Therefore, this review summarizes relevant literature on mosquito-borne viruses metabolomics, with a particular focus on elucidating the metabolic characteristics of cells infected by orthoflaviviruses. By conducting a comparative analysis of the metabolomics data from different sample sources infected with DENV, ZIKV, and JEV, we found that several metabolic pathways involved in viral infection, replication, and pathogenesis are commonly disrupted in the metabolomics data of these orthoflaviviruses. These pathways include the reprogramming of lipid metabolism, interference with energy metabolism, and the induction of host inflammatory responses. These findings identify key targets for subsequent mechanistic studies on the persistent replication and transmission of orthoflaviviruses in mosquito vectors and their ability to cause severe pathology in human hosts. Further elucidations of the above mechanisms could provide an effective scheme for preventing orthoflaviviral transmission in mosquito vectors and treating orthoflaviviral infections. In addition, studying these metabolomic changes in human hosts of orthoflaviviral infections may be able to provide relevant biomarkers for accurate diagnosis of the disease.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"251"},"PeriodicalIF":4.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and characterization of a novel bacteriophage PUTH1 active against Pseudomonas aeruginosa.","authors":"Qizhao Tan, Jing Ye, Tengjiao Zhu, Yun Tian","doi":"10.1186/s12985-025-02859-8","DOIUrl":"10.1186/s12985-025-02859-8","url":null,"abstract":"","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"248"},"PeriodicalIF":4.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Slow virologic control but strong immune and metabolic recovery with dolutegravir-anchored therapy in an HIV cohort in Ghana.","authors":"Mark Appeaning, Edwin Magomere, Alberta Mawulawoe Abotsi, Nana Ama Yeboaa Amoako, Kirk Elorm Kouffie, Becky Ewurama Tetteh, Bridget Nana Darkoa Quist, Christèle Nguepou Tchopba, Gloria Akosua Ansa, Evelyn Yayra Bonney, Peter Kojo Quashie","doi":"10.1186/s12985-025-02873-w","DOIUrl":"10.1186/s12985-025-02873-w","url":null,"abstract":"<p><strong>Introduction: </strong>The West African HIV/AIDS epidemic, historically driven by HIV-1 CRF02_AG, other recombinant forms and HIV-2, remains less researched for various preventive and therapeutic interventions. We established the WACCBIP long-term HIV Infection Cohort (WHICH Study) to investigate the dynamics of HIV epidemic in Ghana. This report evaluates viral load dynamics, immune responses, and organ-level metabolic changes following antiretroviral therapy (ART) initiation.</p><p><strong>Method: </strong>We collected blood samples, medical, and demographic data from ART-naïve individuals at baseline and six months post-ART, and from ART-experienced individuals at a single time point. Participants, aged 10 years and above, were purposively enrolled from six health facilities. Laboratory analyses included viral load, CD4 and CD8 counts, co-infection screening (hepatitis B/C, syphilis), liver and kidney function tests, haemoglobin estimation, and HIV-1/2 typing. Chi-square and logistic regression analyses were used to assess associations between participant demographics and clinical data with uncontrolled viremia and immune recovery.</p><p><strong>Results: </strong>A total of 426 participants were recruited, comprising 159 ART-naïve and 267 ART-experienced individuals, with a mean age of 41.5 years. Median ART duration for ART-experienced was greater than 5 years. Infections included HIV-1 (78.6%), HIV-2 (2.1%), and dual HIV-1&2 (19.2%). Common comorbidities were anaemia (54.9%), hepatitis B (9.5%), and hypertension (8.2%). Most participant (97.9%) were on dolutegravir-anchored regimen. Among ART-naïve individuals, median viral load decreased from log₁₀ 5.16 at baseline to log₁₀ 4.64 copies/mL after six months (p = 0.0156). Median viral load for the ART-experienced arm was log₁₀ 3.23 copies/mL. Median CD4 count increased from 290 cells/mm³ in ART-naïve participants to 504 cells/mm³ at six-months post-ART (p = 0.0003) and 581 cells/mm³ in ART-experienced participants (p < 0.0001). ART-naïve participants were 19 times more likely to have unsuppressed viral loads at baseline compared to ART-experienced participants. ARTnaïve- participants had significantly decreased odds of immune recovery (aOR = 0.35, 95% CI: 0.140-0.85, p = 0.021), as did those with low CD4/CD8 ratio (aOR = 0.06, 95% CI: 0.02-0.20; p < 0.001). Kidney function and haemoglobin levels were significantly improved six-month post-ART among the ART-naïve group.</p><p><strong>Conclusion: </strong>This study highlights the significant reduction in viral load and improved immune recovery following ART initiation despite uncontrolled viremia in a subset of participants. This cohort presents an opportunity to study Ghana's local HIV epidemic, including HIV-1 and HIV-2, and impact of ART on disease progression.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"247"},"PeriodicalIF":4.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small molecule UCM05 inhibits HSV-2 infection via targeting viral glycoproteins and fatty acid synthase with potentiating antiviral immunity.","authors":"Songshan Li, Minghan Li, Yantong Cai, Jun Xian, Rongrong Zhu, Chan Yang, Xin Zhang, Shuya Ren, Aijiao Yu, Shuwen Liu, Bin Yang","doi":"10.1186/s12985-025-02867-8","DOIUrl":"10.1186/s12985-025-02867-8","url":null,"abstract":"<p><p>Herpes simplex virus type 2 (HSV-2) is a highly prevalent human pathogen worldwide that not only causes genital herpes but is also associated with severe health complications, such as neonatal infections and increased susceptibility to HIV. Currently, due to the lack of an effective HSV-2 vaccine and the emergence of more drug-resistant strains, there is an urgent need to develop effective, safe, and affordable anti-HSV-2 medications. The small molecule UCM05 is a novel inhibitor of fatty acid synthase (FASN) and filamentous temperature-sensitive protein Z (Ftsz), with antitumor and antibacterial effects. In this study, we found that UCM05 effectively inhibits both HSV-2 and acyclovir-resistant HSV-2 infections in vitro, significantly improves survival rates in HSV-2-infected mice, and effectively reduces viral titers in tissues. Further, we discovered that UCM05 destroys the membrane integrity of viral particles by directly binding with HSV-2 glycoproteins gB and gD and reduces viral replication by inhibiting viral protein synthesis and fatty acid synthesis. Additionally, UCM05 treatment promoted the generation of type I IFN related genes but does not result in an inflammatory cytokine storm triggered by HSV-2, and it also exhibited activity against co-infection with HIV-1/HSV-2, as well as infection with HSV-1. Overall, our research demonstrates that UCM05 can effectively inhibit HSV-2 infection both in vitro and in vivo. UCM05 represents a potential new antiviral drug against HSV-2.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"249"},"PeriodicalIF":4.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen protects against postpartum Concanavalin A-induced hepatitis by promoting intrahepatic CD4⁺CD25⁺ Treg expansion through activation of the PI3K/Akt signaling pathway in HBV-Tg mice.","authors":"Chuanlu Xu, Yao Su, Wenjing Lu, Jiaqi Dong, Luyao Wang, Yabing Mi, Xinrui Jia, Wenqi Lv, Shengyu Wu, Yuanhui Jia, Hao Ying","doi":"10.1186/s12985-025-02879-4","DOIUrl":"10.1186/s12985-025-02879-4","url":null,"abstract":"<p><strong>Introduction: </strong>Postpartum hepatitis flares have been commonly described, but the specific mechanism is unclear.</p><p><strong>Objectives: </strong>Our objective was to explore estrogen's role in postpartum hepatitis flares in HBV transgenic mice.</p><p><strong>Methods: </strong>The numbers of intrahepatic CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) and the levels of the inhibitory cytokine IL-10 were determined in concanavalin A (Con A)-injected mice with and without estrogen injection postpartum. The role of intrahepatic CD4⁺CD25⁺Foxp3⁺Tregs in suppressing immune responses was investigated by systemically depleting intrahepatic CD25⁺ cells in mice treated with an anti-CD25 mAb. We employed the PI3K inhibitor LY294002 to investigate the function of the PI3K/Akt pathway in regulating the suppressive activity of intrahepatic CD4⁺CD25⁺Foxp3⁺Tregs in vivo.</p><p><strong>Results: </strong>A higher percentage of CD4⁺CD25⁺Foxp3⁺Tregs accumulated in the liver with increasing physiological E2 levels during pregnancy, declined sharply by day 7 postpartum. We discovered that estrogen regulates the proliferation and activation of intrahepatic CD4⁺CD25⁺Foxp3⁺ Tregs via the PI3K/Akt signaling cascade and participates in hepatitis immune regulation. Furthermore, E2 administration postpartum increased intrahepatic CD4⁺CD25⁺Foxp3⁺Tregs and inhibitory cytokine IL-10, which inhibit the immune clearance of CD8⁺ T cells and NK cells along with decreased cytotoxic cytokine IFN-γ and TNF-α levels.</p><p><strong>Conclusion: </strong>Estrogen protects against postpartum Con A-induced hepatitis by promoting intrahepatic CD4⁺CD25⁺ Treg expansion through activation of the PI3K/Akt signaling pathway in HBV-Tg mice.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"245"},"PeriodicalIF":4.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}