Viruses-BaselPub Date : 2025-09-18DOI: 10.3390/v17091260
Austin Nelson, Mario Mietzsch, Jane Hsi, Julia Eby, Paul Chipman, Robert McKenna
{"title":"Structural and Functional Characterization of Porcine Adeno-Associated Viruses.","authors":"Austin Nelson, Mario Mietzsch, Jane Hsi, Julia Eby, Paul Chipman, Robert McKenna","doi":"10.3390/v17091260","DOIUrl":"10.3390/v17091260","url":null,"abstract":"<p><p>Current gene therapy treatments utilizing adeno-associated virus (AAV) vectors are based on capsids of primate origin. However, pre-existing neutralizing anti-AAV antibodies, that are present in a significant portion of the population, can lead to vector inactivation and reduced therapeutic efficacy. Advances in DNA sequencing have facilitated the discovery of many AAVs from non-primate species, including isolates from pigs, which exhibit up to 50% capsid protein sequence divergence, compared to primate AAV serotypes. In this study, AAVs isolated from porcine tissues (AAVpo.1 and AAVpo.6) were selected for structural characterization due to their low capsid protein VP1 sequence identity compared to each other and to AAV9. The AAV vectors were produced via the standard triple transfection system in HEK293 cells using AAV2 <i>rep</i> to package AAV2-ITR vector genomes and were purified by iodixanol density gradient ultracentrifugation. The capsid structures of AAVpo.1 and AAVpo.6 were determined using cryo-electron microscopy and then compared to each other in addition to the AAV5 and AAV9 structures. Given that porcine AAVpo.6 has been reported to infect human cells and the ability to cross the blood-brain barrier, the functional characterization was focused on the identification of a potential glycan receptor utilized by the porcine capsids. Additionally, the porcine AAV capsid reactivity to human derived anti-AAV antibodies was assessed to evaluate the potential for these capsids to be used as alternative vectors for gene therapy, particularly for patients with pre-existing immunity to primate-derived AAV serotypes.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180150","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}
Viruses-BaselPub Date : 2025-09-18DOI: 10.3390/v17091263
Xueling Zheng, Yinyan Zhou, Yue Yu, Shi Cheng, Feifei Cao, Zhou Sun, Jun Li, Xinfen Yu
{"title":"Neutral Impact of SARS-CoV-2 Coinfection on the Recombination-Driven Evolution of Endemic HCoV-OC43.","authors":"Xueling Zheng, Yinyan Zhou, Yue Yu, Shi Cheng, Feifei Cao, Zhou Sun, Jun Li, Xinfen Yu","doi":"10.3390/v17091263","DOIUrl":"10.3390/v17091263","url":null,"abstract":"<p><p>Knowledge gaps exist on whether SARS-CoV-2 co-infection alters recombination frequency or induces phylogenetic incongruities in endemic β-coronaviruses (HCoV-OC43, HCoV-HKU1), limiting our understanding of cross-species evolution. Among 7213 COVID-19 and 1590 non-COVID-19 acute respiratory cases (2021-2022) screened via multiplex PCR, β-coronavirus co-infections (SARS-CoV-2 + HCoV-OC43/HKU1) and single HCoV-OC43/HKU1 infections were identified. Whole-genome sequencing (Illumina NovaSeq) was performed. Phylogenies were reconstructed using Bayesian inference (MrBayes). Recombination was assessed via Bootscan analysis (SimPlot). Co-infection prevalence was low (0.51%, mainly HCoV-HKU1: 0.28%, HCoV-OC43: 0.11%). HCoV-OC43 diverged into lineage 1 (genotype K) and a novel recombinant lineage 2 (genotypes F/J/G/I segments), exhibiting accelerated evolution. HCoV-HKU1 remained genetically stable (genotype B). Co-infection status did not influence evolutionary outcomes. While SARS-CoV-2 co-infection may favor transmission of endemic HCoVs, their evolution appears driven by population-level selection, not co-infection. HCoV-OC43 underwent recombination-driven diversification, contrasting sharply with HCoV-HKU1's stasis, highlighting distinct evolutionary strategies. Integrated genomic and clinical surveillance is critical for tracking coronavirus adaptation.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180109","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":"Mpox Epidemics: A Call to Restore Humanity's Lost Herd Immunity to Orthopoxviruses.","authors":"Misaki Wayengera, Henry Kyobe-Bosa, Winters Muttamba, Olushayo Oluseun Olu, Abdou Salam Gueye, Nicaise Ndembi, Neema Kamara, Morenike Oluwatoyin Folayan, Bruce Kirenga, Sitong Luo, Qingyu Li, Chikwe Ihekweazu","doi":"10.3390/v17091257","DOIUrl":"10.3390/v17091257","url":null,"abstract":"<p><p>Global efforts to eradicate smallpox-an Orthopoxvirus infection-began in the mid-20th century, with the last naturally occurring case reported in 1977. This was achieved through global solidarity efforts that expanded the smallpox eradication vaccination program. Approximately 50 years following the cessation of mass smallpox vaccination and in the absence of access to a sustainable boosting program, the population immunologically naïve to Orthopoxviruses has increased significantly. With increasing global movements and travels, we argue that the emergence of two back-to-back yet distinct mpox epidemics in the 21st century is a sign of humanity's lost herd immunity to Orthopoxviruses. This needs concerted efforts to restore.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180028","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":"Rapid Visual Detection of Senecavirus A Based on RPA-CRISPR/Cas12a System with Canonical or Suboptimal PAM.","authors":"Xinrui Zhao, Genghong Jiang, Qinyi Ruan, Yunjie Qu, Xiaoyu Yang, Yongyan Shi, Dedong Wang, Jianwei Zhou, Jue Liu, Lei Hou","doi":"10.3390/v17091264","DOIUrl":"10.3390/v17091264","url":null,"abstract":"<p><p>Senecavirus A (SVA) is an emerging pathogen responsible for vesicular lesions and neonatal mortality in swine. In the absence of effective vaccines or therapeutics, early and accurate diagnosis is essential for controlling SVA outbreaks. Although nucleic acid-based detection methods are commonly employed, there remains a pressing need for rapid, convenient, highly sensitive, and specific diagnostic tools. Here, we developed a two-pot assay combining recombinase polymerase amplification (RPA) with CRISPR/Cas12a containing crRNA targeting canonical protospacer adjacent motifs (PAMs) for simple, rapid, and visual identification of SVA in clinical samples. Subsequently, we successfully streamlined this system into a one-pot assay by selecting a specially designed crRNA targeting suboptimal PAM and integrating RPA amplification reagents and CRISPR/Cas12a detection components into a single reaction system in one tube. The developed methods exhibited diagnostic specificity, showing no cross-reactivity with four major swine viruses, while showing remarkable sensitivity with a lower detection limit of just two copies. Clinical validation in field samples using these two methods revealed perfect agreement (100% concordance) with conventional quantitative PCR (qPCR) results (sample size, <i>n</i> = 28), with both assays completing detection within 30 min. These results demonstrate that both the one-pot and two-pot RPA-CRISPR/Cas12a assays offer a reliable and efficient method for detecting SVA in this pilot study. Despite the limited sample size, the assays combine rapid reaction time with high sensitivity and specificity, showing great potential for future diagnostic applications.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180099","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":"Porcine Parvovirus in China: Recent Advances, Epidemiology, and Vaccine Strategies.","authors":"Yunchao Liu, Yumei Chen, Yanli Shang, Xiuli Deng, Huifang Hao","doi":"10.3390/v17091262","DOIUrl":"10.3390/v17091262","url":null,"abstract":"<p><p>Porcine parvovirus (PPV), a non-envelope single-stranded DNA virus, causes severe reproductive disorders in swine worldwide, characterized by fetal mortality, mummification, and reduced boar fertility. As a highly prevalent pathogen in Chinese swine herds, PPV imposes substantial economic burdens on intensive pig production systems. This review systematically synthesizes recent advances in PPV virology, focusing on genomic evolution of emerging strains (PPV1-PPV8), epidemiological dynamics of emerging strains, molecular pathogenesis, and novel diagnostic tools. Furthermore, we critically evaluate current vaccine strategies, highlighting their limitations in cross-protective efficacy and viral shedding control. By integrating multi-omics insights with immunological profiling, this work delineates actionable pathways for next-generation vaccine design and proposes a roadmap for rational antigen selection. This review consolidates foundational knowledge and establishes a translational bridge between basic virology and prevention and control of porcine parvovirus, addressing critical gaps in porcine reproductive disease management.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180117","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":"Comparative Performance of Digital PCR and Real-Time RT-PCR in Respiratory Virus Diagnostics.","authors":"Irene Bianconi, Giovanna Viviana Pellecchia, Elisabetta Maria Incrocci, Fabio Vittadello, Maira Nicoletti, Elisabetta Pagani","doi":"10.3390/v17091259","DOIUrl":"10.3390/v17091259","url":null,"abstract":"<p><p><i>Background</i>: Respiratory viral infections pose a major global health burden, and molecular diagnostics such as Real-Time RT-PCR have revealed frequent co-infections. However, precise quantification of viral RNA remains challenging. Digital PCR (dPCR) offers absolute quantification without standard curves and may improve diagnostic accuracy. This study compares dPCR and Real-Time RT-PCR in detecting and quantifying influenza A, influenza B, respiratory syncytial virus (RSV), and SARS-CoV-2 during the 2023-2024 tripledemic. <i>Methods</i>: A total of 123 respiratory samples were analysed and stratified by cycle threshold (Ct) values into high, medium, and low viral load categories. Both dPCR and Real-Time RT-PCR were used to quantify and compare viral loads across these categories. <i>Results</i>: dPCR demonstrated superior accuracy, particularly for high viral loads of influenza A, influenza B, and SARS-CoV-2, and for medium loads of RSV. It showed greater consistency and precision than Real-Time RT-PCR, especially in quantifying intermediate viral levels. <i>Conclusions</i>: These findings highlight the potential of dPCR to enhance respiratory virus diagnostics and support a better understanding of co-infection dynamics. Nonetheless, its routine implementation is currently limited by higher costs and reduced automation compared to Real-Time RT-PCR.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179899","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}
Viruses-BaselPub Date : 2025-09-18DOI: 10.3390/v17091258
Joaquim Pinto Nunes Neto, Daniel Damous Dias, Bruna Laís Sena do Nascimento, Sandro Patroca da Silva, Sâmia Luzia Sena da Silva, Lúcia Aline Moura Reis, Hanna Carolina Farias Reis, Fábio Silva da Silva, Lucas Henrique da Silva E Silva, Durval Bertram Rodrigues Vieira, Roberto Carlos Feitosa Brandão, Wallace Oliveira Rosário, Francisco Amilton Dos Santos Paiva, José Wilson Rosa Júnior, Bruno Tardelli Diniz Nunes, Lívia Carício Martins, Lívia Medeiros Neves Casseb, Ana Cecília Ribeiro Cruz
{"title":"Molecular Detection of Yellow Fever Virus in <i>Haemagogus janthinomys</i> Mosquitoes (Diptera: Culicidae) in a Rural Settlement in the State of Pará, Brazilian Amazon, 2024.","authors":"Joaquim Pinto Nunes Neto, Daniel Damous Dias, Bruna Laís Sena do Nascimento, Sandro Patroca da Silva, Sâmia Luzia Sena da Silva, Lúcia Aline Moura Reis, Hanna Carolina Farias Reis, Fábio Silva da Silva, Lucas Henrique da Silva E Silva, Durval Bertram Rodrigues Vieira, Roberto Carlos Feitosa Brandão, Wallace Oliveira Rosário, Francisco Amilton Dos Santos Paiva, José Wilson Rosa Júnior, Bruno Tardelli Diniz Nunes, Lívia Carício Martins, Lívia Medeiros Neves Casseb, Ana Cecília Ribeiro Cruz","doi":"10.3390/v17091258","DOIUrl":"10.3390/v17091258","url":null,"abstract":"<p><p>Yellow fever (YF) is an acute and potentially fatal hemorrhagic disease caused by the Yellow Fever virus (YFV), endemic to sub-Saharan Africa and several tropical countries, including Brazil. In Brazil, the Amazon region is considered the main endemic area. YFV is maintained in a sylvatic cycle involving Neotropical primates and mosquitoes of the genera <i>Haemagogus</i> and <i>Sabethes</i>, acting as primary and secondary vectors, respectively. In March 2024, entomovirological surveillance was conducted in Santa Bárbara do Pará, Pará, Brazil. A total of 286 mosquitoes were collected, classified into 13 species across nine genera, and grouped into 33 pools. Seventeen pools were tested by RT-qPCR for <i>Orthoflavivirus</i> (YFV, DENV, WNV, SLEV), <i>Alphavirus</i> (CHIKV, MAYV), and <i>Orthobunyavirus</i> (OROV). YFV was detected in four <i>Haemagogus janthinomys</i> pools, with Ct values ranging from 22.2 to 27.9. Metagenomic sequencing confirmed the presence of YFV with assigned reads and >99% protein identity. Notably, the detection occurred without human cases or primate deaths, enabling timely vaccination of the local population. These findings confirm YFV circulation in forested areas of the Belém metropolitan region and reaffirm <i>Hg. janthinomys</i> as a key vector. Our study reinforces the relevance of early entomovirological surveillance and preventive strategies, such as vaccination, to mitigate yellow fever reemergence.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179987","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}
Viruses-BaselPub Date : 2025-09-18DOI: 10.3390/v17091261
Adeline Goulet, Jennifer Mahony, Douwe van Sinderen, Christian Cambillau
{"title":"Predicted Structures of <i>Ceduovirus</i> Adhesion Devices Highlight Unique Architectures Reminiscent of Bacterial Secretion System VI.","authors":"Adeline Goulet, Jennifer Mahony, Douwe van Sinderen, Christian Cambillau","doi":"10.3390/v17091261","DOIUrl":"10.3390/v17091261","url":null,"abstract":"<p><p>Bacteriophages, or phages, are sophisticated nanomachines that efficiently infect bacteria. Their infection of lactic acid bacteria (LAB) used in fermentation can lead to significant industrial losses. Among phages that infect monoderm bacteria, those with siphovirion morphology characterized by a long, non-contractile tail are predominant. The initial stage of phage infection involves precise host recognition and binding. To achieve this, phages feature host adhesion devices (HADs) located at the distal end of their tails, which have evolved to recognize specific proteinaceous or saccharidic receptors on the host cell wall. <i>Ceduovirus</i> represents a group of unique lytic siphophages that specifically infect the LAB <i>Lactococcus lactis</i> by targeting proteinaceous receptors. Despite having compact genomes, most of their structural genes are poorly annotated and the architecture and function of their HADs remain unknown. Here we used AlphaFold3 to explore the <i>Ceduovirus</i> HADs and their interaction with the host. We show that <i>Ceduovirus</i> HADs exhibit unprecedented features among bacteriophages infecting Gram<sup>+</sup>, share structural similarities with bacterial secretion system VI, and combine both saccharide and protein-binding modules. Moreover, we could annotate the majority of <i>Ceduovirus</i> genes encoding structural proteins by leveraging their predicted structures, highlighting AlphaFold's significant contribution to phage genome annotation.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180133","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}
Viruses-BaselPub Date : 2025-09-17DOI: 10.3390/v17091255
Laura Sneller, Keshav Mathur, Shyam Kottilil, Poonam Mathur
{"title":"Hot and Cold HCC: Uncoupling Viral Oncogenesis and Therapy.","authors":"Laura Sneller, Keshav Mathur, Shyam Kottilil, Poonam Mathur","doi":"10.3390/v17091255","DOIUrl":"10.3390/v17091255","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is rising in incidence globally. It is the sixth most common cancer and the third leading cause of cancer-related mortality worldwide. Infection with hepatitis B and/or C virus is a significant risk factor for developing HCC. These viruses exert their carcinogenicity in both direct and indirect ways, including induction of immune exhaustion with prolonged antigen exposure. Therefore, the best therapeutic option for HCC is prevention, i.e., Hepatitis B vaccination and treatment of viral hepatitis. However, when HCC develops because of viral hepatitis or other etiologies, long-lasting effects on the immune system remain even after viral suppression, which affect the response to HCC therapy. Recent studies have suggested a \"hot\" and \"cold\" model for HCC, in which the two kinds of HCC tumors have very distinct tumor microenvironments. The microenvironment for hot HCC makes these tumors amenable to immunotherapy with checkpoint inhibitors. Therefore, converting cold HCC tumors to hot tumors may make them susceptible to immunotherapy. In this review, we provide an overview of HCC epidemiology and prevention, an overview of tumor microenvironments of hot and cold HCC, the proposed mechanisms for converting cold tumors to hot tumors, and a concise summary of the evidence for combination checkpoint inhibitor therapy for HCC.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180024","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}
Viruses-BaselPub Date : 2025-09-17DOI: 10.3390/v17091256
Tang-Her Jaing, Yi-Lun Wang, Tsung-Yen Chang
{"title":"BK Polyomavirus-Associated Nephropathy and Hemorrhagic Cystitis in Transplant Recipients-What We Understand and What Remains Unclear.","authors":"Tang-Her Jaing, Yi-Lun Wang, Tsung-Yen Chang","doi":"10.3390/v17091256","DOIUrl":"10.3390/v17091256","url":null,"abstract":"<p><p>The reactivation of BK polyomavirus (BKPyV) during severe immunosuppression plays a crucial role in two significant syndromes observed in transplant recipients: BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant patients and BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) in hematopoietic cell transplant (HCT) recipients. This review aims to summarize the current understanding and lingering ambiguity by looking at three primary questions: (1) In cases with BKPyV-related illnesses in transplant patients, which diagnostic methods have the best track record of accuracy and success? (2) Which therapy approaches have the best track records of safety and efficacy in real-world clinical settings? (3) What can immunological research teach us about the development of future tailored treatments? Diagnosis involves the patient's appearance, ruling out other potential causes, and employing quantitative PCR to identify active viral replication in urine or plasma. BKPyV-HC can vary from self-limited hematuria to potentially fatal bleeding, while BKPyVAN may lead to loss and dysfunction of the allograft. Reducing immunosuppression remains the key aspect of treatment. However, the effectiveness of antivirals (such cidofovir and leflunomide) is not always the same, and supporting measures depend on the syndrome. Researchers are looking into new immunotherapies, such as virus-specific cytotoxic T cells. Due to the intricate viro-immunopathology and lack of defined treatment regimens, future initiatives should focus on prospective studies to establish validated thresholds, enhance management algorithms, and integrate immune surveillance into individualized therapy.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179963","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}