Yifei Jin, Xiang Li, Huan Cui, Cheng Zhang, Yanrui Li, Heng Wang, Yan Wang, Yixin Zhao, Zhixin Yang, Yan Zhang, Zhongyi Wang
{"title":"Environmental Adaptability of Influenza A(H9N2) Virus in the Process of Genetic Evolution.","authors":"Yifei Jin, Xiang Li, Huan Cui, Cheng Zhang, Yanrui Li, Heng Wang, Yan Wang, Yixin Zhao, Zhixin Yang, Yan Zhang, Zhongyi Wang","doi":"10.1002/jmv.71127","DOIUrl":"10.1002/jmv.71127","url":null,"abstract":"<p><p>Understanding the transmission routes of avian influenza viruses (AIVs) is critical for outbreak control. Beyond direct contact and aerosol transmission, indirect transmission via contaminated environmental surfaces contributes to exposure risk, particularly in live poultry markets (LPMs). Although previous studies have examined the environmental persistence of individual AIV strains, systematic comparisons among genetically related viruses remain scarce. H9N2, designated by the WHO as a potential \"Pathogen X,\" is of particular concern. Here, we assessed the environmental persistence and indirect transmission potential of four genetically related H9N2 AIVs originating from the same LPM-associated epidemiological context: one human isolate (H19) and three LPM environmental isolates (E01, E02, E03). All viruses exhibited temperature-dependent infectivity decay on four surface materials. Notably, H19 and E01 demonstrated prolonged environmental persistence compared with E02 and E03 under multiple conditions. Moreover, smooth, non-porous surfaces (plastic, glass, stainless steel) generally supported longer viral survival than porous non-woven fabric. In a guinea pig model, H19 and E01 led to detectable indirect transmission, whereas E02 and E03 did not. Comparative sequence analysis revealed differences at NP-346 and PB2-18 between these two phenotypic groups, although the functional relevance of these substitutions remains to be determined. Collectively, these findings reveal that environmental persistence and indirect transmission potential can vary markedly among genetically related LPM-associated H9N2 AIVs, supporting the integration of environmental adaptability into routine risk assessment frameworks.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 9","pages":"e71127"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887842","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}
Juan Gao, Mengying Ma, Yaya Zhang, Xin Wang, Rui Li, Juan Xue, Xuemei Ren, Zhuo Li
{"title":"Comparative Analysis of NAT, TRFIA, and ELISA for Screening Blood-Borne Pathogens in Preoperative and Pre-Transfusion Patients.","authors":"Juan Gao, Mengying Ma, Yaya Zhang, Xin Wang, Rui Li, Juan Xue, Xuemei Ren, Zhuo Li","doi":"10.1002/jmv.71125","DOIUrl":"10.1002/jmv.71125","url":null,"abstract":"<p><p>This retrospective single-center study compared nucleic acid testing (NAT), time-resolved fluorescence immunoassay (TRFIA), and enzyme-linked immunosorbent assay (ELISA) for screening hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Treponema pallidum (TP) among 1243 preoperative and pre-transfusion patients. Specimens were detected by pathogen-targeted NAT, serological TRFIA and routine ELISA panels, respectively. HBV positive rates were 2.17% (NAT), 2.09% (TRFIA) and 1.53% (ELISA); HCV positive rates were 0.08%, 0.24% and 0.08%, without statistical intergroup differences (all p > 0.05). TRFIA yielded a significantly higher TP positive rate than ELISA (0.88% versus 0.40%, p < 0.05), while no HIV-positive specimens were identified in this cohort. Kappa tests showed moderate-to-good consistency for HBV (0.711-0.842) and perfect concordance between NAT and ELISA for HCV (Kappa = 1.000). Twenty-three discordant samples were found, including eight NAT-only HBV positives suggestive of potential window-period infections and six TRFIA-only TP positives. Limited by an obstetric-female-dominated cohort, scarce HCV cases, and zero HIV positives, standard diagnostic accuracy metrics could not be comprehensively evaluated. NAT and TRFIA exhibit complementary screening values, yet their combined application may increase false-positive risks and lacks systematic cost-effectiveness evidence to support large-scale clinical implementation.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 9","pages":"e71125"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880480","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}
Nabeel Alzahrani, Rfeef Alyami, Zainab BuAli, Omniya Fallatah, Samer Zakri, Ahmed Alnujaim, Mohammad Bosaeed, Turki Abujamel, Anwar M. Hashem, Sameera Al Johani
{"title":"Genomic Characterization of Influenza B Victoria Lineage Viruses Circulating in Saudi Arabia During the 2024–2025 Season","authors":"Nabeel Alzahrani, Rfeef Alyami, Zainab BuAli, Omniya Fallatah, Samer Zakri, Ahmed Alnujaim, Mohammad Bosaeed, Turki Abujamel, Anwar M. Hashem, Sameera Al Johani","doi":"10.1002/jmv.71128","DOIUrl":"https://doi.org/10.1002/jmv.71128","url":null,"abstract":"<div>\u0000 \u0000 <p>Influenza B viruses contribute substantially to global morbidity and mortality, yet genomic data from the Middle East remain limited. We retrospectively performed whole-genome sequencing of six influenza B virus-positive residual nasopharyngeal specimens collected at King Abdulaziz Medical City, Riyadh, during the 2024–2025 season, including one fatal pediatric case, and described their genomic features alongside clinical outcomes. All six genomes belonged to the B/Victoria lineage and clustered within V1A.3a.2-derived subclades circulating globally during 2024–2025. Five genomes, including the fatal pediatric case, were assigned to subclade C.5.6, whereas one non-fatal case belonged to C.5.7. The Saudi sequences were interspersed among contemporaneous reference strains from Europe, Asia, and North America, without evidence of a distinct local lineage. The fatal isolate did not occupy a distinct phylogenetic position and contained none of the screened virulence-associated markers, including the neuraminidase N342K substitution. These genomes provide regional surveillance data from an underrepresented setting. Given the small sample size and inclusion of a single fatal case, the findings are descriptive and do not permit inference regarding genomic determinants of disease severity. Larger studies integrating viral genomic, clinical, and host data are needed.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 9","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Siyu Feng, Mingzhi Pan, Luyu Wang, Changyi Ji, Ze Xiang, Jian Wu, Mengmeng Gu
{"title":"PYGL as a Novel Biomarker for Disease Progression and Prognosis in HEV-ALF Patients.","authors":"Siyu Feng, Mingzhi Pan, Luyu Wang, Changyi Ji, Ze Xiang, Jian Wu, Mengmeng Gu","doi":"10.1002/jmv.71126","DOIUrl":"10.1002/jmv.71126","url":null,"abstract":"<p><p>Hepatitis E virus (HEV) is a significant cause of acute liver failure (ALF). The role of glycogen phosphorylase L (PYGL) in the diagnosis and prognosis of HEV-ALF remains unclear. This study collected clinical data and baseline characteristics from HEV-ALF patients, acute hepatitis E (AHE) patients, and healthy controls (HCs), measuring serum PYGL levels in each group. Methods including Orthogonal partial least squares discriminant analysis (OPLS-DA), receiver operating characteristic (ROC) and decision curve analysis (DCA) were used to evaluate the clinical utility of PYGL. Results showed that PYGL effectively diagnosed HEV-ALF (AUC = 0.911). PYGL levels were significantly higher in HEV-ALF patients than in AHE patients and HCs (p < 0.001). Among HEV-ALF patients, non-survivors exhibited higher PYGL levels than survivors (p < 0.001). PYGL demonstrated good predictive ability for 30-day mortality (AUC = 0.859). OPLS-DA and DCA confirmed its strong decision-making utility. Furthermore, PYGL levels escalated with increasing organ failure and paralleled clinical worsening, being highest in the deterioration group (p < 0.05). PYGL is a potential diagnostic and prognostic biomarker in HEV-ALF patients, where elevated levels indicate poorer outcomes and support early intervention.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 9","pages":"e71126"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874514","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":"Comprehensive Viral Detection and Profiling of Plasma Cell-Free RNA in Patients With Suspected Hemophagocytic Lymphohistiocytosis","authors":"Yuto Fukuda, Kazuhiro Horiba, Masanori Hashino, Shinji Kawabe, Hiroki Miura, Yoshiki Kawamura, Makito Tanaka, Takako Suzuki, Yuka Torii, Hideki Muramatsu, Yoshiyuki Takahashi, Tetsushi Yoshikawa, Jun-ichi Kawada","doi":"10.1002/jmv.71122","DOIUrl":"https://doi.org/10.1002/jmv.71122","url":null,"abstract":"<p>Hemophagocytic lymphohistiocytosis (HLH) is a severe, rapidly progressive disease. While viral infection is considered a common etiology of pediatric HLH, specific causative viruses other than the Epstein-Barr virus (EBV) have been rarely identified. This study utilized metagenomic next-generation sequencing (NGS) to identify potential causative pathogens in plasma samples from 17 pediatric patients with suspected HLH. Additionally, one case each of confirmed EBV- and cytomegalovirus (CMV)-associated HLH was analyzed for methodological validation. Plasma cell-free RNA (cfRNA) profiling was performed using NGS data to assess the host transcriptome response. Significant viral reads of human herpesvirus-6B, human herpesvirus-7, and Hubei reo-like virus (HRLV) 14 were detected using metagenomic NGS in one patient each. Plasma cfRNA profiles from five patients with viral infection (including EBV and CMV) were compared to those of 14 patients without viral infection. By comparing the two patient groups, 1053 differentially expressed genes were identified. The gene ontology (GO) term of “adaptive immune response” (GO: 0002250) was significantly enriched among upregulated genes in the virus-positive group. Furthermore, an isolated cluster consisting specifically of mitochondrial RNAs, was identified in the upregulated genes of the virus-positive group. Using metagenomic NGS, several candidate viral pathogens were identified in patients with suspected infection-related HLH. The viral genome of HRLV 14, previously undetected in human clinical samples, was identified in one patient. The results from plasma cfRNA profiling suggest that mitochondrial RNAs may reflect the underlying pathogenesis of virus-associated HLH and have potential utility as disease biomarkers.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 9","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.71122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860065","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}
Miao-Miao Xu, Yun-Xin Yao, Hui Lyu, Yu Qian, Zhe-Zhe Tian, Yu-Chen Fan, Kai Wang
{"title":"ICAM-1 Hypomethylation Predicts Poor Prognosis in Patients With Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.","authors":"Miao-Miao Xu, Yun-Xin Yao, Hui Lyu, Yu Qian, Zhe-Zhe Tian, Yu-Chen Fan, Kai Wang","doi":"10.1002/jmv.71118","DOIUrl":"10.1002/jmv.71118","url":null,"abstract":"<p><p>Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with a high short-term mortality rate. Therefore, early and accurate prognostic prediction is crucial for precise clinical management. This study aims to investigate the expression patterns of intercellular adhesion molecule-1 (ICAM-1) and its predictive value for the short-term prognosis of patients with HBV-ACLF. The Methylight method was used to quantitatively detect ICAM-1 promoter methylation level in peripheral blood mononuclear cells (PMBCs) of 286 participants. Meanwhile, the mRNA and plasma expression levels of ICAM-1 were determined using RT-qPCR and ELISA, respectively. The ICAM-1 promoter methylation levels in PBMCs of HBV-ACLF patients were significantly lower than those in chronic hepatitis B (CHB) patients and healthy controls (HCs), whereas the mRNA and plasma expression levels of ICAM-1 were markedly elevated. The ICAM-1 methylation levels in HBV-ACLF patients correlated with specific clinical parameters. Among HBV-ACLF patients, ICAM-1 methylation levels were significantly lower in the non-survivor groups at both 28 and 90 days. The study further revealed that ICAM-1 methylation level serves as an independent influencing factor for the prognosis of HBV-ACLF patients at 28 and 90 days. Based on ROC curve and Kaplan-Meier curves, ICAM-1 methylation levels demonstrated excellent performance in predicting 28- and 90-day mortality in patients with HBV-ACLF. In conclusion, patients with HBV-ACLF exhibit hypomethylation of the ICAM-1 promoter. The combination of ICAM-1 promoter methylation level and MELD score can effectively enhance the predictive ability for the short-term prognosis of HBV-ACLF patients.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 9","pages":"e71118"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891746","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}
Michael X Fu, Maria F Perdomo, Sheila F Lumley, Johan Ringlander, Kai Kean, Kaitlin Reid, Richard Mayne, Oscar Enrique Torres Montaguth, Leysa Forrest, Sarah Buddle, Johannes C Botha, Joakim B Stenbäck, Zachery Dickson, Chris Kent, Haiting Chai, Matthew Byott, Leo Hannolainen, Shannah Secret, George Airey, Klaus Hedman, Monique I Andersson, M Azim Ansari, Eleni Nastouli, Judith Breuer, Philippa C Matthews, Tanya Golubchik, William L Irving, Peter Simmonds, Heli Harvala
{"title":"Next-Generation Sequencing Methods for Sensitive Hepatitis B Viral Genome Analysis: A European Study.","authors":"Michael X Fu, Maria F Perdomo, Sheila F Lumley, Johan Ringlander, Kai Kean, Kaitlin Reid, Richard Mayne, Oscar Enrique Torres Montaguth, Leysa Forrest, Sarah Buddle, Johannes C Botha, Joakim B Stenbäck, Zachery Dickson, Chris Kent, Haiting Chai, Matthew Byott, Leo Hannolainen, Shannah Secret, George Airey, Klaus Hedman, Monique I Andersson, M Azim Ansari, Eleni Nastouli, Judith Breuer, Philippa C Matthews, Tanya Golubchik, William L Irving, Peter Simmonds, Heli Harvala","doi":"10.1002/jmv.71130","DOIUrl":"10.1002/jmv.71130","url":null,"abstract":"<p><p>This multicentre study investigated the utility of next-generation sequencing (NGS) to detect and generate hepatitis B virus (HBV) genomes in samples of low viral load (from 0.2 to 6207 IU/mL). 23 HBV DNA-positive plasma samples of genotypes A-E and one HBV-negative control sample were assayed blindly via 9 established NGS methods from 6 European laboratories. Methods included untargeted metagenomics, pre-enrichment by probe-capture followed by Illumina sequencing, and HBV-specific PCR pre-amplification followed by sequencing with Nanopore or Illumina. Full HBV genomes were obtained only from samples with viral loads > 1000 IU/mL using probe-capture methods, > 200 IU/mL using PCR-Illumina methods, > 10 IU/mL using PCR-Nanopore methods, and in no samples using metagenomic methods. Contamination was observed in the negative control and samples with very low viral loads in PCR-based methods. Probe-capture and metagenomic methods detected additional viruses not routinely screened in blood donations, including polyomaviruses and herpesviruses; positive results were confirmed by PCR. In conclusion, NGS may delineate whole-genome sequences at low viral loads if supported by a PCR pre-amplification step. Probe-capture methods also reliably detect HBV without pre-amplification but show limited genome coverage for samples with low viral loads; they may additionally detect a wide range of blood-borne viruses.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 9","pages":"e71130"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874510","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}
José Valter Joaquim Silva Júnior, Edmilson F de Oliveira-Filho, Jan Felix Drexler
{"title":"Addressing Key Issues in Developing Safe and Effective Oropouche Virus Vaccines.","authors":"José Valter Joaquim Silva Júnior, Edmilson F de Oliveira-Filho, Jan Felix Drexler","doi":"10.1002/jmv.71132","DOIUrl":"10.1002/jmv.71132","url":null,"abstract":"","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 9","pages":"e71132"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891729","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}
Stijn de Man, Evert-Jan Wils, Armand Paauw, Yesim Delice-Ikiz, Wessel Hanselaar, Han J C Veltman, Gerda Doejaaren, Chelton van Laaren, Kim van den Bosch, Vincent Vermeule, Peter de Man, David S Y Ong
{"title":"Airborne Virus Shedding of Respiratory Syncytial Virus Compared to Influenza A Virus in Hospitalized Patients.","authors":"Stijn de Man, Evert-Jan Wils, Armand Paauw, Yesim Delice-Ikiz, Wessel Hanselaar, Han J C Veltman, Gerda Doejaaren, Chelton van Laaren, Kim van den Bosch, Vincent Vermeule, Peter de Man, David S Y Ong","doi":"10.1002/jmv.71114","DOIUrl":"10.1002/jmv.71114","url":null,"abstract":"<p><p>Airborne transmission is an important route for the spread of respiratory viruses. To assess the potential for airborne shedding of influenza A virus (IAV) and respiratory syncytial virus (RSV), this study compared the presence of viral RNA in air samples collected near hospitalized patients. Patients with IAV or RSV infection and a nasopharyngeal swab cycle threshold value of 28 or lower were included. Air sampling was performed using a vacuum cleaner equipped with a detachable soluble air filter attached to the hose inlet. For each patient, one sample was collected 50 cm dorsally and one 50 cm ventrally relative to the patient's face, each for 2 min. Filters were dissolved and analyzed for viral RNA by RT-qPCR. In total, 59 patients were included: 39 with IAV infection and 21 with RSV infection, including one patient co-infected with both viruses. Air samples were more frequently positive in RSV-infected patients than in IAV-infected patients (12/21 [57%] vs. 6/39 [15%], p = 0.0012). In multivariable analysis, RSV-infections remained associated with higher rates of air sample positivity after adjustment for nasopharyngeal viral load. These findings suggest different aerosol shedding between RSV and IAV, although differences in infectious potential remain to be determined.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 9","pages":"e71114"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874519","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":"Identification of a Novel Small Molecule Facilitating HIV Elimination by the “Shock-And-Kill” Approach","authors":"Yuichiro Hara, Haruki Kitamura, Kouki Matsuda, Chieko Fujisaki, Sayaka Sukegawa, Kosuke Tanimoto, Kenji Maeda, Hiroaki Takeuchi","doi":"10.1002/jmv.71131","DOIUrl":"https://doi.org/10.1002/jmv.71131","url":null,"abstract":"<p>Antiretroviral therapy (ART) has markedly improved the prognosis of people living with HIV (PLWH); however, latent viral reservoirs remain a major barrier to a cure. The “Shock and Kill” strategy aims to reactivate latent provirus with latency-reversing agents (LRAs) and subsequently eliminate the infected cells, yet most LRAs characterized to date provide only the “shock” component. Through screening a small-molecule library, we identified 2-hydrido-2,2'-spirobi(1,3,2-benzodioxaphosphole) (2-HSB) as a novel candidate that both reactivates latent HIV provirus and selectively induces cytopathic effects in latently infected reservoir cell lines, thereby exhibiting a dual “Shock and Kill” activity within a single compound. Mechanistically, the HIV-1 <i>tat</i> protein appears to contribute to this selectivity. At the single-cell level, the two effects appeared largely independent, indicating that, under the conditions tested, reactivation was not a consequence of cell death and vice versa. Importantly, 2-HSB induced viral transcription in ex vivo CD4<sup>+</sup> T cells from ART-suppressed PLWH. Together, these findings identify 2-HSB as a dual-action candidate that reactivates latent HIV-1 and preferentially induces cytopathic effects in reservoir cell-line models, while supporting further mechanistic and ex vivo validation in primary reservoir-bearing cells.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 9","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.71131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860161","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}