Virology Journal最新文献

{"title":"Identification of key genes associated with T cell exhaustion in HIV infection based on transcriptomic data.","authors":"Yan Zhang, Yutao Yong, Wenqing Liu, Die Hu, Chengjie Ji, Chunyu Ma","doi":"10.1186/s12985-026-03243-w","DOIUrl":"10.1186/s12985-026-03243-w","url":null,"abstract":"<p><strong>Background: </strong>Human immunodeficiency virus (HIV) is a lentivirus belonging to the retrovirus subclass. HIV specifically targets and infects human CD4 + T lymphocytes, and T cell exhaustion (TEX) plays an important role in disease progression. However, the specific molecular mechanisms have not been fully elucidated. In this study, we explored the potential mechanisms by analyzing transcriptomic data and TEX-related genes, and screened novel markers closely associated with HIV neutralization and T cell function to assess TEX severity and guide precise immunotherapy.</p><p><strong>Methods: </strong>Transcriptomic data related to HIV were screened from public databases. Key genes associated with TEX were identified through machine learning, receiver operating characteristic curve analyses, and gene expression analyses, and a molecular regulatory network was constructed. Subsequently, methods such as localization analysis, gene set enrichment analysis, and immune infiltration analysis were employed to explore the underlying mechanisms. Finally, the mRNA expression of diagnostic genes in clinical samples was verified by RT-qPCR.</p><p><strong>Results: </strong>EPSTI1 and MSC were identified as key genes. EPSTI1 was enriched in the Epstein-Barr virus infection pathway, whereas MSC was associated with base excision repair. MSC protein was mainly localized in the nucleus, while the subcellular localization of EPSTI1 remained unclear. Immune infiltration analysis revealed the significant differential infiltration of 12 cell types, among which MSC was associated with three cell types and EPSTI1 was associated with one cell type. RT-qPCR results further suggested that EPSTI1 expression was significantly elevated in HIV-infected individuals, and its upregulation was likely positively correlated with the severity of TEX. No statistically significant difference was observed in MSC expression between the two groups.</p><p><strong>Conclusion: </strong>This study indicated that EPSTI1 may serve as a potential functional gene during HIV infection. EPSTI1 may be a promising candidate biomarker for TEX in HIV infection and could act as a tentative therapeutic target for follow-up research.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424606","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":"Revisiting HPV integration landscapes using telomere-to-telomere human genome reference closes the gaps in HPV integration sites search.","authors":"Alicja Pacholewska, Bushra Yusuf Khan, Michal R Schweiger","doi":"10.1186/s12985-026-03241-y","DOIUrl":"10.1186/s12985-026-03241-y","url":null,"abstract":"<p><p>Accurate characterization of human papillomavirus (HPV) integration into the host genome is essential for understanding HPV-driven carcinogenesis. However, most previous integration studies relied on incomplete human reference genomes, potentially obscuring integration events occurring within highly repetitive genomic regions. Here, we reassessed HPV integration landscapes using the first complete telomere-to-telomere (T2T) human reference genome assembly (hs1). We reanalyzed datasets from three independent studies generated using complementary sequencing technologies, including short-read Illumina sequencing, PacBio continuous long reads (CLR), PacBio high-fidelity (HiFi) sequencing, and ultra-long Oxford Nanopore sequencing. Reanalysis using the T2T reference confirmed the majority of previously reported integration breakpoints while identifying numerous additional sites, increasing the total number of detected breakpoints from 446 to 799. Notably, newly detected integrations frequently localized to repeat-rich genomic regions, including centromeric and pericentromeric satellite sequences that were absent from earlier reference assemblies. Importantly, integration events within these regions were detectable not only in long-read datasets but also in short-read sequencing data when analyzed using the complete reference genome. Our findings demonstrate that incomplete reference assemblies have led to systematic underestimation of HPV integration events, particularly within structurally complex genomic regions. These results highlight the importance of adopting complete human genome references for viral integration analyses and suggest that reanalysis of existing datasets may reveal previously overlooked biologically and clinically relevant integration events.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"23 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977885","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":"Evaluating the safety profile of poliomyelitis vaccines: insights from post-marketing surveillance.","authors":"Gang Qiu, Xiao-Dong Ma, Feng-Feng Fu","doi":"10.1186/s12985-026-03244-9","DOIUrl":"10.1186/s12985-026-03244-9","url":null,"abstract":"<p><p>Poliomyelitis (POLIO) vaccines are widely used because of their high clinical effectiveness and minimal side effects.However, as post-marketing surveillance data have been collected, several serious adverse events (SAEs) linked to poliomyelitis vaccination have been reported.Currently, there is a lack of quantitative studies using real-world data, and detailed information about these adverse events is scarce.To fill this gap, adverse event signals associated with the poliomyelitis vaccine were extracted and analyzed using U.S. data.The Vaccine Adverse Event Reporting System (VAERS) serves as an important resource for post-marketing vaccine safety surveillance.Various statistical methods, such as the reporting odds ratio (ROR), the Proportional Reporting Ratio (PRR) approach, and the Bayesian Confidence Propagation Neural Network (BCPNN), were utilized to identify adverse event signals linked to poliomyelitis vaccination.Positive signals corresponding to designated medical events (DMEs) were identified for in-depth comparison and analysis.An analysis of 60,710 adverse events related to the poliomyelitis vaccine revealed 342 positive signals across 25 System Organ Classifications, with the most frequent being General disorders and administration site conditions.Three potential positive new signals consistent with Preferred Terms (PTs) were identified in DME: Erythema multiforme, Dermatitis exfoliative and Anaphylactoid reaction. This study identified disproportionality signals for erythema multiforme, exfoliative dermatitis, and anaphylactoid reaction in VAERS reports following poliomyelitis vaccination. These findings represent statistical reporting associations rather than evidence of causality and should be interpreted as hypothesis-generating signals requiring confirmation in well-designed epidemiological studies. Prompt clinical evaluation is recommended if severe or persistent symptoms occur.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148406095","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":"Cellular receptors and host factors mediating orthoflavivirus entry.","authors":"Shuangshuang Yang, Meng Zhang, Xingyong Yang, Jinxi Yue, Xue Li, Peiyue Zhang, Hong Zhang","doi":"10.1186/s12985-026-03239-6","DOIUrl":"10.1186/s12985-026-03239-6","url":null,"abstract":"<p><p>Orthoflaviviruses are positive-sense, enveloped RNA viruses that include dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV), West Nile virus (WNV), and Japanese encephalitis virus (JEV). Viral entry is a multistep process governed by the envelope (E) glycoprotein, virion lipid composition, and host-cell molecules that act at distinct mechanistic stages. A major limitation of the current literature is that attachment factors, internalization receptors, immune-modulatory receptors, and membrane-associated cofactors are often collectively termed \"receptors\", which can obscure the strength and interpretation of the underlying evidence. This review therefore reorganizes reported orthoflavivirus entry-associated molecules into four functional classes: attachment factors, bona fide or candidate internalization receptors, indirect immune-modulatory receptors, and membrane-associated or post-entry cofactors. We place particular emphasis on DENV because it imposes a major clinical burden among orthoflaviviruses and has been the subject of the most extensive receptor-related research. By integrating evidence from binding assays, genetic loss-of-function studies, and in vivo models, this review highlights conserved and virus-specific entry mechanisms. This mechanism-based framework may guide the development of receptor decoys and host-targeting antivirals, although clinical translation will require rigorous validation of antiviral breadth, delivery, safety, and resistance potential.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148406123","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 associated fatty liver disease induced hepatocyte apoptosis to eliminate hepatitis B virus.","authors":"Jiayu Yu, Xin Zheng","doi":"10.1186/s12985-026-03218-x","DOIUrl":"10.1186/s12985-026-03218-x","url":null,"abstract":"<p><strong>Backgroud and aim: </strong>With the rising prevalence of chronic hepatitis B (CHB) co-occurring with metabolic dysfunction-associated fatty liver disease (MAFLD), an in-depth investigation into the impact and mechanisms of MAFLD on CHB is urgently needed. Prior studies have reported that patients with concomitant CHB and MAFLD exhibit lower levels of hepatitis B virus (HBV) replication; however, the underlying mechanistic basis remains unclear. Accumulating evidence indicates that induction of apoptosis is a critical mechanism for HBV clearance. Therefore, it remains to be determined whether lipotoxicity-induced hepatocyte apoptosis contributes significantly to the accelerated elimination of HBV. To investigate the effects and underlying mechanisms of fatty acids against HBV in HepG2.2.15 cells.</p><p><strong>Methods: </strong>Human liver transcriptome data were used to analyze biological changes in CHB patients with MAFLD compared to those with CHB alone. In vitro, palmitic acid (PA) was used to simulate lipotoxicity in HepG2.2.15 cells, and oleic acid (OA) was used to reverse the effects of PA. The levels of HBsAg, HBeAg, and HBV-DNA in cell supernatants and lysates were detected by ELISA and PCR. Mitochondrial membrane permeability, oxidative stress, and apoptosis were evaluated to investigate the potential mechanisms of PA's effects on HepG2.2.15 cells.</p><p><strong>Results: </strong>Human hepatic transcriptome enrichment analysis showed upregulated apoptosis-related pathways and downregulated mitochondrial/redox genes in patients with comorbid CHB and MASH. Cell experiments showed that PA reduced the levels of HBsAg, HBeAg, and HBV-DNA in HepG2.2.15 cell supernatants and lysates. The underlying mechanism is that PA increased mitochondrial membrane permeability and ROS levels to activate Caspase-9, PARP, and Caspase-3, thereby inducing apoptosis. However, the unsaturated fatty acid OA restored mitochondrial function, reduced oxidative stress and apoptosis, and reversed HBV antigen levels.</p><p><strong>Conclusion: </strong>PA activates the mitochondrial apoptotic pathway to promote HBV clearance, while OA can reverse this effect. This study provides new evidence for the interaction mechanism between CHB and MAFLD and suggests new treatment strategies for patients with this comorbidity.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148413022","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":"Spatiotemporal dynamics of Zika in Brazil, 2016-2023: a nationwide population-based study.","authors":"Marcos César de Souza Santos, Paula Esbaltar de Oliveira, Phoebe Silva van Emmerik, Rafael Pedro de Souza Nascimento, Vanessa Cardoso Pereira, Sávio Luiz Pereira Nunes, Havandécio Rodrigues de Matos Júnior, Chirles Araújo de França, Adeilton Gonçalves da Silva Junior, Thais Silva Matos, Marcio Bezerra Santos, Carla Pacheco Teixeira, Diana Paola Gutierrez Diaz de Azevedo, Daniel Elías Cuartas Arroyave, José Valter Joaquim Silva Júnior, Rodrigo Feliciano Carmo, Carlos Dornels Freire de Souza","doi":"10.1186/s12985-026-03233-y","DOIUrl":"10.1186/s12985-026-03233-y","url":null,"abstract":"<p><strong>Introduction: </strong>The Zika epidemic was first reported in Brazil in 2015. Since then, several factors have sustained the virus transmission chain in the country. This study aimed to describe the epidemiological profile and temporal trends, as well as to identify significant spatial and spatiotemporal clusters of Zika in Brazil between 2016 and 2023.</p><p><strong>Methods: </strong>Ecological study including confirmed Zika cases in Brazil from 2016 to 2023. Data were extracted from the National Notifiable Diseases Information System. Sociodemographic variables (age, sex, race/ethnicity, education level, and pregnancy status) were collected, along with incidence rates. Analyses were conducted in three steps: (1) description of the epidemiological profile; (2) temporal analysis: Joinpoint regression modeling was applied to identify trends and the Average Annual Percent Change (AAPC) was calculated with 95% confidence intervals and 5% significance level; (3) spatial analysis: spatial dependence among municipalities was assessed using the Global Moran's I index, followed by spatial scan statistics to identify spatial clusters of virus transmission, using both purely spatial and spatiotemporal analyses.</p><p><strong>Results: </strong>A total of 176,122 cases were reported during the study period. Among them, 42.27% (n = 74,458) were aged 20-39 years, 66.96% (n = 117,945) were female, and 34.92% (n = 61,513) were mixed-race. A decreasing trend in incidence rates was observed in Brazil (AAPC - 36.55%; p < 0.001), with disparities across states. Fifteen out of 27 states showed a downward trend. Rio Grande do Norte was the only state to exhibit an increasing incidence trend and was also identified as the area with the highest relative risk of Zika infection in the country (RR = 12.1; p < 0.001). In the spatio-temporal analysis, the cluster with the highest relative risk (RR 31.08; p < 0.001) included 2,770 municipalities across the North, Northeast, Southeast, and Central-West regions.</p><p><strong>Conclusion: </strong>Zika cases predominated among adults, females, and mixed-race individuals. In Brazil, the overall incidence rate showed a decreasing trend during the study period. The Northeast and Central-West regions had the largest number of clusters, highlighting the need to strengthen surveillance activities in these areas to reduce transmission rates.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412998","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":"Association between serum calcium and in-hospital mortality in patients with severe fever with thrombocytopenia syndrome: a retrospective cohort study.","authors":"Huan Wang, Sisi Fang, Hua Wang, Xin Zheng","doi":"10.1186/s12985-026-03232-z","DOIUrl":"10.1186/s12985-026-03232-z","url":null,"abstract":"<p><strong>Objective: </strong>Severe fever with thrombocytopenia syndrome (SFTS) is a viral infectious disease characterized by high mortality. Calcium dysregulation is implicated in viral replication and host immune response. We aimed to evaluate the association between serum calcium levels and in-hospital mortality in patients with SFTS.</p><p><strong>Methods: </strong>In this retrospective, single-centre cohort study, we enrolled 809 laboratory-confirmed SFTS patients admitted between April 2017 and June 2024. Hypocalcemia was defined as corrected calcium < 8.12 mg/dL. Multivariate logistic regression, restricted cubic spline (RCS), and longitudinal analyses were employed to assess associations between serum calcium and mortality.</p><p><strong>Results: </strong>The in-hospital mortality rate was 11.87% (96/809). Hypocalcemia was observed in 72.68% of patients (588/809) with SFTS upon admission. Multivariate logistic regression analysis revealed that lower serum calcium was an independent predictor of in-hospital mortality, alongside older age, neurological symptoms, higher viral loads, lower albumin levels, elevated creatinine, and prolonged activated partial thromboplastin time (APTT). Restricted cubic spline (RCS) analysis suggested a visual L-shaped pattern between serum calcium levels and in-hospital mortality, but without statistically significant evidence of non-linearity. Dynamic analysis showed that serum calcium levels increased and normalized by day 6 in survivors but peaked and declined thereafter in non-survivors. Hypocalcemia was independently associated with hypoalbuminemia, hypoglobulinemia, hyponatremia, and monocytopenia. Furthermore, serum calcium levels were inversely correlated with viral load, creatine kinase, APTT, IL-6, and IL-10 (all p < 0.05).</p><p><strong>Conclusions: </strong>Hypocalcemia is exceedingly common in SFTS patients and serves as a robust, independent prognostic marker for in-hospital mortality. Its association with high viral replication and host inflammatory response underscores its clinical significance. Serial monitoring of serum calcium may serve as a useful marker for risk stratification in SFTS.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148406113","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":"Coxsackievirus A6 infection exacerbates kidney injury in mice through the p38-MAPK pathway.","authors":"Tiantian Sun, Wenjie Jiang, Guangcai Duan, Dong Li, Wangquan Ji, Shuaiyin Chen, Haiyan Yang, Fang Wang, Shouhang Chen, Yuefei Jin, Peiyu Zhu, Mingjie Sun","doi":"10.1186/s12985-026-03236-9","DOIUrl":"10.1186/s12985-026-03236-9","url":null,"abstract":"<p><p>Severe hand, foot, and mouth disease (HFMD) poses a risk of serious multi-organ complications in children. While renal dysfunction has been observed in some cases, detailed investigations on kidney injury and molecular mechanisms remain limited. Coxsackievirus A6 (CVA6) has emerged as a major pathogen responsible for HFMD. To reveal the underlying pathways of CVA6-associated renal injury, we enrolled 90 children diagnosed with CVA6 infection and 45 healthy children. The levels of uric acid (UA), creatinine (CREA) and UREA in the serum were measured. We found that serum levels of UA, CREA, and UREA were significantly elevated in CVA6-infected children compared to healthy children. Subsequently, a previously established mouse model of CVA6 infection was used to assess urinary retention, kidney inflammation, and histopathological changes. Consistent with the clinical findings, infected mice exhibited increased CREA, UREA, and UA levels, urinary retention, and renal inflammation. Electron microscopy revealed glomerular atrophy and basement membrane thickening in CVA6-infected mice, accompanied by reduced expression of VEGF, Occludin, and VE-cadherin. Furthermore, complement deposition was also observed in glomeruli and renal tubules. Finally, CVA6 infection significantly increased phospho-p38 levels in mouse kidneys. To investigate the role of the p38-MAPK signaling pathway in CVA6-induced renal injury, we treated the CVA6-infected mice with PD169316, a specific inhibitor of p38/MAPK signaling pathway, and observed that the kidney injury in the treated group was alleviated. Overall, our findings highlight a critical role for the p38 phosphorylation in CVA6-induced renal injury, and provide new insights into the management of severe HFMD-associated kidney complications.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148406110","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":"ADAM17 blockade restores natural killer cell antibody-dependent cytotoxicity against human immunodeficiency virus-1.","authors":"Sho Sugawara, Stephanie Jost, Griffin Woolley, R Keith Reeves","doi":"10.1186/s12985-026-03223-0","DOIUrl":"10.1186/s12985-026-03223-0","url":null,"abstract":"<p><p>Natural killer (NK) cells are critical innate effector cells against human immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis. Among the diverse NK cell functions, antibody-dependent cellular cytotoxicity (ADCC) is the most critical for HIV-1 control. Nevertheless, multiple reports have demonstrated dysfunctional NK cell activity in people living with HIV-1 (PLWH), including impaired ADCC. As a putative mechanism, CD16 signaling activation in PLWH is perturbed via ADAM17-mediated CD16 downregulation, and ADAM17 blockade can reverse CD16 downregulation in PLWH NK cells. However, the link between elevated ADAM17 function and diminished HIV-1-specific NK cell ADCC has remained unclear. Thus, to fill this knowledge gap, we tested whether ADAM17 perturbation can restore HIV-1-specific NK cell ADCC. We demonstrated that inhibition of ADAM17 can restore HIV-1-specific ADCC by recovering surface CD16 expression. Furthermore, we observed that PLWH NK cells experience impaired ADCC associated with ADAM17 elevation. Altogether, we found that ADAM17 blockade can restore impaired NK cell ADCC against HIV-1, and this approach could be applied to further advance NK cell-based immunotherapeutics toward an HIV-1 cure. These findings establish ADAM17 as a tractable checkpoint to enhance Fc‑effector responses and support the integration of ADAM17 targeting into NK‑cell-based HIV cure strategies.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397957","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":"A receptor-Fc based SFV replicon Trim-Away platform for targeted viral protein degradation.","authors":"Yiming Han, Qisheng Dong, Zhen Tian, Xiaodi Wang, Pengbo Wang, Quanyong Liu, Yangxue Liu, Qi Guo, Shoutao Zhang","doi":"10.1186/s12985-026-03235-w","DOIUrl":"10.1186/s12985-026-03235-w","url":null,"abstract":"<p><strong>Background: </strong>Developing effective antiviral strategies is urgently needed during global viral pandemics. Traditional approaches, including small-molecule inhibitors, neutralizing antibodies, and RNA interference (RNAi), often face challenges such as drug resistance, limited specificity, and inefficient delivery. These limitations highlight the pressing need for innovative strategies focused on the targeted degradation of viral proteins.</p><p><strong>Methods: </strong>We developed an optimized Trim-Away system employing a receptor-Fc fusion protein strategy. This system integrates the E3 ubiquitin ligase TRIM21 with engineered receptor-Fc proteins to ensure highly specific recognition and intracellular degradation. A key innovation is the use of the Semliki Forest virus (SFV) self-amplifying replicon (pSFV). This platform enables sustained and robust expression of the Trim-Away components. Furthermore, this plasmid-based delivery eliminates the need for protein purification, thereby streamlining the process and improving delivery efficiency.</p><p><strong>Results: </strong>The system effectively degrades diverse viral targets. Specifically, it successfully degraded the spike proteins of both wild-type SARS-CoV-2 and its Omicron variant. It also targeted adeno-associated virus (AAV) capsid proteins. In vivo assays further confirmed that the self-amplifying replicon markedly reduces AAV-encoded luciferase expression. These data demonstrate that the system maintains high potency even at low dosages.</p><p><strong>Conclusions: </strong>Our findings demonstrate that the pSFV-driven Trim-Away system is a powerful tool for viral protein degradation. The receptor-Fc strategy provides a significant advantage against rapidly mutating viruses. This study establishes a versatile and adaptable platform for future antiviral intervention.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388008","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}