Pub Date : 2026-03-21DOI: 10.1016/j.virusres.2026.199717
Irene Ferreiro, Joaquín Hurtado, Alfredo Bruno, Juan Cristina
Avian Influenza Viruses (AIVs) pose today a very significant risk to global health given the widespread circulation of H5N1 highly pathogenic avian influenza viruses (HPAIV). After decimating the avian population all over the world, these viruses spill over to many different mammal species, causing also fatal outbreaks. As the virus continues to evolve increasing human cases of H5N1 HPAIV have been reported, causing concern that these viruses may adapt to the human host and became a pandemic new virus. In order to gain insight into this matter, a detailed phylogenetic analysis of H5N1 HPAIV isolated from humans was performed. A significant number of substitutions have been found in the hemagglutinins (HA) and neuraminidases (NA) among the three H5N1 clades already detected in human cases. Some of these substitutions were found to produce changes in the 3D structure of these proteins. Substitutions providing an evolutionary advantage to replicate or evade the immune response in mammals have been found in several non-structural proteins of strains infecting humans, including regulatory proteins, like PA-X or PB1-F2. A significant degree of polymorphic sites was observed in the proteins of the polymerase complex. The results of these studies are discussed in terms of the evolution of H5N1 HPAIV infecting humans and future work to be done to address the pandemic potential of these viruses.
{"title":"On the brink of emergence: an evolutionary approach to Influenza A virus H5N1 isolated from humans.","authors":"Irene Ferreiro, Joaquín Hurtado, Alfredo Bruno, Juan Cristina","doi":"10.1016/j.virusres.2026.199717","DOIUrl":"https://doi.org/10.1016/j.virusres.2026.199717","url":null,"abstract":"<p><p>Avian Influenza Viruses (AIVs) pose today a very significant risk to global health given the widespread circulation of H5N1 highly pathogenic avian influenza viruses (HPAIV). After decimating the avian population all over the world, these viruses spill over to many different mammal species, causing also fatal outbreaks. As the virus continues to evolve increasing human cases of H5N1 HPAIV have been reported, causing concern that these viruses may adapt to the human host and became a pandemic new virus. In order to gain insight into this matter, a detailed phylogenetic analysis of H5N1 HPAIV isolated from humans was performed. A significant number of substitutions have been found in the hemagglutinins (HA) and neuraminidases (NA) among the three H5N1 clades already detected in human cases. Some of these substitutions were found to produce changes in the 3D structure of these proteins. Substitutions providing an evolutionary advantage to replicate or evade the immune response in mammals have been found in several non-structural proteins of strains infecting humans, including regulatory proteins, like PA-X or PB1-F2. A significant degree of polymorphic sites was observed in the proteins of the polymerase complex. The results of these studies are discussed in terms of the evolution of H5N1 HPAIV infecting humans and future work to be done to address the pandemic potential of these viruses.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":" ","pages":"199717"},"PeriodicalIF":2.7,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-20DOI: 10.1016/j.virusres.2026.199716
Haidi Karam-Allah Ramadan, Aml A Rayan, Zeinab R Mohamed, Mohammed Ezz-Eldin, Ahmed A Kotb, Mohamed Ahmed, Rasha Assad Assiri, Salwa Seif Eldin, Amal A Elkhawaga
Background: Leucocytes cell population data (CPD) parameters have been applied in diagnosis and prognosis of viral infections. We aim to explore pattern of leucocytes CPD in people living with HIV (PLWH) and its role in clinical stratification.
Methods: This study included treatment-naïve PLWH and healthy control. Clinical HIV stages were determined. Laboratory assessment was conducted using complete blood picture, CPD, CD4+ T cells count, and HIV RNA testing. Correlation between CPD with CD4+ and HIV RNA was evaluated.
Results: A total of 125 were recruited; 70 cases and 55 control. Age and gender were not significantly different. WHO stage 3 was predominant at 34.29% and half of PLWH had advanced HIV. CPD parameters of neutrophils, lymphocytes and monocytes composition were significantly higher in PLWH. Parameters of neutrophils nucleic acid contents, lymphocytes dispersion of nucleic acid contents, and both neutrophils and lymphocytes size were significantly higher in PLWH. CD4+ T cells count positively correlated with WBCs, lymphocytes and monocytes count and size, but negatively correlated with lymphocytes composition, nucleic acid contents, and size, and both monocytes and neutrophils composition and nucleic acid contents. Viral load negatively correlated with neutrophils size.
Conclusion: CPD can be a cost-effective quantitative tool reflecting immune depletion in HIV. By decoding these parameters, clinicians can stratify PLWH risk of disease progression beyond CD4+ T cells count and viral load.
{"title":"First Report on Leucocytes Cell Population Data as an Applicable Test for Clinical Stratification in People Living with HIV.","authors":"Haidi Karam-Allah Ramadan, Aml A Rayan, Zeinab R Mohamed, Mohammed Ezz-Eldin, Ahmed A Kotb, Mohamed Ahmed, Rasha Assad Assiri, Salwa Seif Eldin, Amal A Elkhawaga","doi":"10.1016/j.virusres.2026.199716","DOIUrl":"https://doi.org/10.1016/j.virusres.2026.199716","url":null,"abstract":"<p><strong>Background: </strong>Leucocytes cell population data (CPD) parameters have been applied in diagnosis and prognosis of viral infections. We aim to explore pattern of leucocytes CPD in people living with HIV (PLWH) and its role in clinical stratification.</p><p><strong>Methods: </strong>This study included treatment-naïve PLWH and healthy control. Clinical HIV stages were determined. Laboratory assessment was conducted using complete blood picture, CPD, CD4+ T cells count, and HIV RNA testing. Correlation between CPD with CD4+ and HIV RNA was evaluated.</p><p><strong>Results: </strong>A total of 125 were recruited; 70 cases and 55 control. Age and gender were not significantly different. WHO stage 3 was predominant at 34.29% and half of PLWH had advanced HIV. CPD parameters of neutrophils, lymphocytes and monocytes composition were significantly higher in PLWH. Parameters of neutrophils nucleic acid contents, lymphocytes dispersion of nucleic acid contents, and both neutrophils and lymphocytes size were significantly higher in PLWH. CD4+ T cells count positively correlated with WBCs, lymphocytes and monocytes count and size, but negatively correlated with lymphocytes composition, nucleic acid contents, and size, and both monocytes and neutrophils composition and nucleic acid contents. Viral load negatively correlated with neutrophils size.</p><p><strong>Conclusion: </strong>CPD can be a cost-effective quantitative tool reflecting immune depletion in HIV. By decoding these parameters, clinicians can stratify PLWH risk of disease progression beyond CD4+ T cells count and viral load.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":" ","pages":"199716"},"PeriodicalIF":2.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Varroa mite (Varroa destructor) has reshaped the viral landscape of honey bee colonies, significantly contributing to colony mortality. In response, Varroa-resistant honey bee breeding programs have developed as a promising and sustainable long-term strategy to control Varroa mite infestations in managed colonies. These breeding programs drive the coevolution of hygienic bees and Varroa mites, however the impact of such coevolution on bee and mite viral dynamics remains poorly understood. To address this gap, we investigated how Varroa-resistant traits influence the tripartite interaction among honey bees, Varroa mites, and viruses. Two apiaries were established: one in Greensboro, North Carolina, consisting of high and low UBeeO colonies, and another in Stoneville, Mississippi, consisting of Pol-line and Commercial colonies. Worker bees and Varroa mites were collected from each colony throughout the beekeeping season and screened for 7 viruses. Hygienic selection significantly reduced the Varroa mite infestation level and influenced the dynamics of viruses in worker bees and Varroa mites. Specifically, titers of Varroa-associated viruses were significantly reduced in worker bees and in mites collected from hygienic colonies. Additionally, hygienic selection altered the co-occurrence patterns and correlations among multiple critically important viruses in mites and worker bees. These findings highlight the value of selective breeding as an effective strategy for improving honey bee health and colony survival and shed light on the complex tripartite relationships between honey bees, Varroa mites, and viruses.
{"title":"Honey bee hygienic selection impacts virus dynamics of both bees and Varroa mites.","authors":"Esmaeil Amiri, Somayeh Mehrparvar, Bita Valizadeh, Kaira Wagoner","doi":"10.1016/j.virusres.2026.199715","DOIUrl":"https://doi.org/10.1016/j.virusres.2026.199715","url":null,"abstract":"<p><p>The Varroa mite (Varroa destructor) has reshaped the viral landscape of honey bee colonies, significantly contributing to colony mortality. In response, Varroa-resistant honey bee breeding programs have developed as a promising and sustainable long-term strategy to control Varroa mite infestations in managed colonies. These breeding programs drive the coevolution of hygienic bees and Varroa mites, however the impact of such coevolution on bee and mite viral dynamics remains poorly understood. To address this gap, we investigated how Varroa-resistant traits influence the tripartite interaction among honey bees, Varroa mites, and viruses. Two apiaries were established: one in Greensboro, North Carolina, consisting of high and low UBeeO colonies, and another in Stoneville, Mississippi, consisting of Pol-line and Commercial colonies. Worker bees and Varroa mites were collected from each colony throughout the beekeeping season and screened for 7 viruses. Hygienic selection significantly reduced the Varroa mite infestation level and influenced the dynamics of viruses in worker bees and Varroa mites. Specifically, titers of Varroa-associated viruses were significantly reduced in worker bees and in mites collected from hygienic colonies. Additionally, hygienic selection altered the co-occurrence patterns and correlations among multiple critically important viruses in mites and worker bees. These findings highlight the value of selective breeding as an effective strategy for improving honey bee health and colony survival and shed light on the complex tripartite relationships between honey bees, Varroa mites, and viruses.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":" ","pages":"199715"},"PeriodicalIF":2.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17DOI: 10.1016/j.virusres.2026.199714
Lóránt Hatvani, Sakae Hisano, Hideki Kondo, Hitomi Sugahara, Paul Telengech, Sabitree Shahi, Sarah Remi Ibiang, Sándor Kocsubé, Tünde Kartali, David A Fitzpatrick, Helen Grogan, Nobuhiro Suzuki
Dry bubble disease, attributed to the filamentous fungus Lecanicillium fungicola (Cordycipitaceae) results in huge yield losses in mushroom (Agaricus bisporus) cultivation worldwide. The possibilities for controlling the disease using commercial fungicides are highly limited, and therefore, there is an increasing demand for novel, alternative means of pest management. Our research objective was the comprehensive examination of viruses in the causal agents of dry bubble disease, which may open up an avenue for its virocontrol in the future. Out of 57 fungal isolates obtained from dry bubble-affected A. bisporus crops in various countries, 47 (82%) were confirmed by ITS (Internal Transcribed Spacer) sequence analysis as L. fungicola. In addition, different members of the genera Akanthomyces and Simplicillium (7 and 3 isolates, respectively), yet unknown to cause dry bubble symptoms, have also been detected. Cellulose column chromatography revealed the presence of double-stranded (ds) RNA in seven L. fungicola and three Akanthomyces sp. isolates, suggesting viral infection. The ten dsRNA-positive and eight randomly selected dsRNA-negative fungal strains were subjected to rRNA-depletion high-throughput RNA-sequencing analysis. The presence of seven new viruses representing four new species in the established families, Partitiviridae, Polymycoviridae, Botourmiaviridae and the narna-like virus group, and three previously established/proposed species in the families Chrysoviridae and "Mycovirgaviridae" were confirmed. The impact of the detected and identified viruses on their host fungi, and their potential applicability for virocontrol purposes will be examined in the future. This study provides the first detailed report on viruses of mushroom pathogenic fungi.
{"title":"Virome of the fungi associated with mushroom dry bubble disease.","authors":"Lóránt Hatvani, Sakae Hisano, Hideki Kondo, Hitomi Sugahara, Paul Telengech, Sabitree Shahi, Sarah Remi Ibiang, Sándor Kocsubé, Tünde Kartali, David A Fitzpatrick, Helen Grogan, Nobuhiro Suzuki","doi":"10.1016/j.virusres.2026.199714","DOIUrl":"https://doi.org/10.1016/j.virusres.2026.199714","url":null,"abstract":"<p><p>Dry bubble disease, attributed to the filamentous fungus Lecanicillium fungicola (Cordycipitaceae) results in huge yield losses in mushroom (Agaricus bisporus) cultivation worldwide. The possibilities for controlling the disease using commercial fungicides are highly limited, and therefore, there is an increasing demand for novel, alternative means of pest management. Our research objective was the comprehensive examination of viruses in the causal agents of dry bubble disease, which may open up an avenue for its virocontrol in the future. Out of 57 fungal isolates obtained from dry bubble-affected A. bisporus crops in various countries, 47 (82%) were confirmed by ITS (Internal Transcribed Spacer) sequence analysis as L. fungicola. In addition, different members of the genera Akanthomyces and Simplicillium (7 and 3 isolates, respectively), yet unknown to cause dry bubble symptoms, have also been detected. Cellulose column chromatography revealed the presence of double-stranded (ds) RNA in seven L. fungicola and three Akanthomyces sp. isolates, suggesting viral infection. The ten dsRNA-positive and eight randomly selected dsRNA-negative fungal strains were subjected to rRNA-depletion high-throughput RNA-sequencing analysis. The presence of seven new viruses representing four new species in the established families, Partitiviridae, Polymycoviridae, Botourmiaviridae and the narna-like virus group, and three previously established/proposed species in the families Chrysoviridae and \"Mycovirgaviridae\" were confirmed. The impact of the detected and identified viruses on their host fungi, and their potential applicability for virocontrol purposes will be examined in the future. This study provides the first detailed report on viruses of mushroom pathogenic fungi.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":" ","pages":"199714"},"PeriodicalIF":2.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-02DOI: 10.1016/j.virusres.2026.199699
Xinyi Yu , Yan Dai , Xuewen Ji , Qinqin Pu , Ruonan Zhang , Mengqi Shi , Nannan Hu , Ke Jin , Jin Zhu , Jun Li
Background
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high mortality and limited therapeutic options. Poly(rC)-binding protein 2 (PCBP2) is a multifunctional RNA-binding protein involved in post-transcriptional regulation and innate immune modulation. Although PCBP2 has been reported to negatively regulate antiviral signaling in other viral infections, its role in Dabie bandavirus (DBV) infection remains unclear.
Methods
Single-cell transcriptomic analysis was performed to characterize PCBP2 mRNA expression across immune cell populations in peripheral blood. PCBP2 expression levels were further examined in DBV-infected clinical samples, IFNAR⁻/⁻ mouse models, and THP-1 cells using quantitative RT-PCR, western blotting, and immunohistochemistry. THP-1 cells with plasmid-mediated PCBP2 overexpression or lentivirus-mediated PCBP2 knockdown were established to investigate the functional role of PCBP2. Activation of the RIG-I-like receptor (RLR) signaling pathway was evaluated by assessing key signaling molecules and downstream interferon responses. The impact of PCBP2 on DBV replication was determined by TCID50 assay, viral nucleoprotein (NP) expression, and immunofluorescence analysis.
Results
PCBP2 expression was significantly downregulated during DBV infection in clinical samples, animal models, and cell cultures, and reduced PCBP2 expression was associated with increased disease severity and unfavorable clinical outcomes. Functional analyses demonstrated that PCBP2 suppressed DBV-induced activation of type I interferon signaling and interferon-stimulated genes, including ISG12a and G1P3. Mechanistically, PCBP2 directly interacted with the mitochondrial antiviral signaling protein MAVS and promoted its K48-linked polyubiquitination, resulting in proteasome-dependent degradation and attenuation of the MAVS-TBK1-IRF3 signaling axis. Consistent with its immunosuppressive role, PCBP2 knockdown significantly reduced DBV replication, whereas PCBP2 overexpression enhanced viral replication in THP-1 cells.
Conclusions
These findings identify PCBP2 as a critical negative regulator of RLR-mediated antiviral signaling during DBV infection. By facilitating MAVS degradation and suppressing innate immune responses, PCBP2 promotes viral replication, providing new insights into DBV immune evasion mechanisms and highlighting PCBP2 as a potential host-directed therapeutic target for SFTS.
{"title":"PCBP2 inhibits antiviral innate immune responses via the MAVS-mediated signaling pathway in severe fever with thrombocytopenia syndrome","authors":"Xinyi Yu , Yan Dai , Xuewen Ji , Qinqin Pu , Ruonan Zhang , Mengqi Shi , Nannan Hu , Ke Jin , Jin Zhu , Jun Li","doi":"10.1016/j.virusres.2026.199699","DOIUrl":"10.1016/j.virusres.2026.199699","url":null,"abstract":"<div><h3>Background</h3><div>Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high mortality and limited therapeutic options. Poly(rC)-binding protein 2 (PCBP2) is a multifunctional RNA-binding protein involved in post-transcriptional regulation and innate immune modulation. Although PCBP2 has been reported to negatively regulate antiviral signaling in other viral infections, its role in Dabie bandavirus (DBV) infection remains unclear.</div></div><div><h3>Methods</h3><div>Single-cell transcriptomic analysis was performed to characterize PCBP2 mRNA expression across immune cell populations in peripheral blood. PCBP2 expression levels were further examined in DBV-infected clinical samples, IFNAR⁻/⁻ mouse models, and THP-1 cells using quantitative RT-PCR, western blotting, and immunohistochemistry. THP-1 cells with plasmid-mediated PCBP2 overexpression or lentivirus-mediated PCBP2 knockdown were established to investigate the functional role of PCBP2. Activation of the RIG-I-like receptor (RLR) signaling pathway was evaluated by assessing key signaling molecules and downstream interferon responses. The impact of PCBP2 on DBV replication was determined by TCID<sub>50</sub> assay, viral nucleoprotein (NP) expression, and immunofluorescence analysis.</div></div><div><h3>Results</h3><div>PCBP2 expression was significantly downregulated during DBV infection in clinical samples, animal models, and cell cultures, and reduced PCBP2 expression was associated with increased disease severity and unfavorable clinical outcomes. Functional analyses demonstrated that PCBP2 suppressed DBV-induced activation of type I interferon signaling and interferon-stimulated genes, including ISG12a and G1P3. Mechanistically, PCBP2 directly interacted with the mitochondrial antiviral signaling protein MAVS and promoted its K48-linked polyubiquitination, resulting in proteasome-dependent degradation and attenuation of the MAVS-TBK1-IRF3 signaling axis. Consistent with its immunosuppressive role, PCBP2 knockdown significantly reduced DBV replication, whereas PCBP2 overexpression enhanced viral replication in THP-1 cells.</div></div><div><h3>Conclusions</h3><div>These findings identify PCBP2 as a critical negative regulator of RLR-mediated antiviral signaling during DBV infection. By facilitating MAVS degradation and suppressing innate immune responses, PCBP2 promotes viral replication, providing new insights into DBV immune evasion mechanisms and highlighting PCBP2 as a potential host-directed therapeutic target for SFTS.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"365 ","pages":"Article 199699"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bovine leukemia virus (BLV), a member of the delta retrovirus family, is transmitted horizontally among cows. BLV causes enzootic bovine leukosis and has great economic impact on the cattle industry. Recently, secretory-defective Env proteins (e.g., Refrex-1 and FeLIX) have been detected in domestic cats and shown to possess antiretroviral activity against gammaretroviruses via viral receptor interference. Therefore, we investigated whether BLV-derived molecules engineered similarly exhibit antiviral activity against BLV infection. We generated several proteins consisting of the BLV envelope surface unit (SU) region and signal peptide, without the transmembrane region, and tested their inhibitory effects on BLV infection. These artificial mutant Env-SU proteins were detected as secreted proteins in cultured cells. Colony formation and quantitative PCR assays revealed that the secreted Env-SU proteins exhibited an inhibitory effect on BLV infection. In conclusion, the engineered BLV Env-SU protein was found to effectively inhibit BLV infection, likely through a mechanism consistent with viral receptor interference and is expected to contribute to the development of infection-prevention methods against BLV.
{"title":"Engineered soluble truncated envelope proteins block bovine leukemia virus infection","authors":"Nashon Wanjala , Ryusuke Matsumoto , Didik Pramono , Ariko Miyake , Kazuo Nishigaki","doi":"10.1016/j.virusres.2026.199701","DOIUrl":"10.1016/j.virusres.2026.199701","url":null,"abstract":"<div><div>Bovine leukemia virus (BLV), a member of the delta retrovirus family, is transmitted horizontally among cows. BLV causes enzootic bovine leukosis and has great economic impact on the cattle industry. Recently, secretory-defective Env proteins (e.g., Refrex-1 and FeLIX) have been detected in domestic cats and shown to possess antiretroviral activity against gammaretroviruses via viral receptor interference. Therefore, we investigated whether BLV-derived molecules engineered similarly exhibit antiviral activity against BLV infection. We generated several proteins consisting of the BLV envelope surface unit (SU) region and signal peptide, without the transmembrane region, and tested their inhibitory effects on BLV infection. These artificial mutant Env-SU proteins were detected as secreted proteins in cultured cells. Colony formation and quantitative PCR assays revealed that the secreted Env-SU proteins exhibited an inhibitory effect on BLV infection. In conclusion, the engineered BLV Env-SU protein was found to effectively inhibit BLV infection, likely through a mechanism consistent with viral receptor interference and is expected to contribute to the development of infection-prevention methods against BLV.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"365 ","pages":"Article 199701"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-28DOI: 10.1016/j.virusres.2026.199693
Zhiyu Li , Huiqin Chen , Zuhao Wang , Xiaodong Liu , Shugen Qu
Oncolytic viruses (OVs) represent a promising immunotherapy for cancer treatment, though their clinical application is often limited by systemic toxicity and low immunogenicity. To address this, we developed NDV-GT, a genetically engineered Newcastle disease virus that encodes porcine α-1,3-galactosyltransferase. These epitopes are recognized by pre-existing natural antibodies, triggering a hyperacute rejection response characterized by complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Furthermore, NDV-GT modulates the tumor microenvironment by promoting T-cell infiltration and cytokine secretion, converting immunologically “cold” tumors into “hot” ones. Mechanistically, the virus inhibits PI3K/AKT and NF-κB signaling pathways, inducing apoptosis and suppressing tumor proliferation. In a preliminary clinical study of 20 patients with advanced refractory carcinomas, NDV-GT achieved a 90.0% disease control rate with no serious adverse events, underscoring its potential as a novel, safe, and effective oncolytic agent that elicits robust antitumor immunity.
{"title":"NDV-GT wth hyperacute rejection in cancer therapy","authors":"Zhiyu Li , Huiqin Chen , Zuhao Wang , Xiaodong Liu , Shugen Qu","doi":"10.1016/j.virusres.2026.199693","DOIUrl":"10.1016/j.virusres.2026.199693","url":null,"abstract":"<div><div>Oncolytic viruses (OVs) represent a promising immunotherapy for cancer treatment, though their clinical application is often limited by systemic toxicity and low immunogenicity. To address this, we developed NDV-GT, a genetically engineered Newcastle disease virus that encodes porcine α-1,3-galactosyltransferase. These epitopes are recognized by pre-existing natural antibodies, triggering a hyperacute rejection response characterized by complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Furthermore, NDV-GT modulates the tumor microenvironment by promoting T-cell infiltration and cytokine secretion, converting immunologically “cold” tumors into “hot” ones. Mechanistically, the virus inhibits PI3K/AKT and NF-κB signaling pathways, inducing apoptosis and suppressing tumor proliferation. In a preliminary clinical study of 20 patients with advanced refractory carcinomas, NDV-GT achieved a 90.0% disease control rate with no serious adverse events, underscoring its potential as a novel, safe, and effective oncolytic agent that elicits robust antitumor immunity.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"365 ","pages":"Article 199693"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-04DOI: 10.1016/j.virusres.2026.199698
Jing Liu, Bingjie Liu, Xia Xie, Xin Yang, Qiong Liu
Despite the clinical possibility of reducing hepatitis B virus (HBV) to almost undetectable levels through nucleotide analogs or interferon, the process of hepatic fibrosis in HBV hepatitis carriers perdures. This study will investigate the function of RAB25 in HBV-induced liver fibrosis and related mechanisms. In the study, the expression level of RAB25 was shown to be increased within liver fibrotic tissue samples in Gene Expression Omnibus (GEO) microarrays (GSE171294 and GSE84044) and clinical samples as well as in HBV-induced hepatic stellate cells (HSCs) activation. Silencing RAB25 inhibited HSCs activation induced by TGF-β1 and HBV-associated hepatocellular carcinoma cells HepG2.2.15, also significantly inhibited HSCs viability, proliferation, and migration and the expression levels of α-SMA, Collagen I, MMP2, and PCNA. However, the overexpression of RAB25 significantly promoted HBV-associated hepatocellular carcinoma cells and TGF-β1-induced HSCs activation. Mechanistically, silencing RAB25 in HSCs significantly repressed PI3K/AKT activation triggered by HBV-associated hepatocellular carcinoma cells. However, the overexpression of RAB25 notably promoted PI3K/AKT activation. In conclusion, silencing of RAB25 inhibits HBV-associated hepatocellular carcinoma cell-induced hepatic fibrosis by suppressing the PI3K/AKT signaling. RAB25 has been proven to be an underlying target for clinical treatment of HBV-associated liver fibrosis.
{"title":"RAB25 promotes hepatitis B virus-induced liver fibrosis progression through activation of the PI3K/AKT signaling pathway","authors":"Jing Liu, Bingjie Liu, Xia Xie, Xin Yang, Qiong Liu","doi":"10.1016/j.virusres.2026.199698","DOIUrl":"10.1016/j.virusres.2026.199698","url":null,"abstract":"<div><div>Despite the clinical possibility of reducing hepatitis B virus (HBV) to almost undetectable levels through nucleotide analogs or interferon, the process of hepatic fibrosis in HBV hepatitis carriers perdures. This study will investigate the function of RAB25 in HBV-induced liver fibrosis and related mechanisms. In the study, the expression level of RAB25 was shown to be increased within liver fibrotic tissue samples in Gene Expression Omnibus (GEO) microarrays (GSE171294 and GSE84044) and clinical samples as well as in HBV-induced hepatic stellate cells (HSCs) activation. Silencing RAB25 inhibited HSCs activation induced by TGF-β1 and HBV-associated hepatocellular carcinoma cells HepG2.2.15, also significantly inhibited HSCs viability, proliferation, and migration and the expression levels of α-SMA, Collagen I, MMP2, and PCNA. However, the overexpression of RAB25 significantly promoted HBV-associated hepatocellular carcinoma cells and TGF-β1-induced HSCs activation. Mechanistically, silencing RAB25 in HSCs significantly repressed PI3K/AKT activation triggered by HBV-associated hepatocellular carcinoma cells. However, the overexpression of RAB25 notably promoted PI3K/AKT activation. In conclusion, silencing of RAB25 inhibits HBV-associated hepatocellular carcinoma cell-induced hepatic fibrosis by suppressing the PI3K/AKT signaling. RAB25 has been proven to be an underlying target for clinical treatment of HBV-associated liver fibrosis.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"365 ","pages":"Article 199698"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-02DOI: 10.1016/j.virusres.2026.199697
Hsiao-En Lin , Ying-Wen Huang , Yi-Chin Lai , Na-Sheng Lin , Yau-Heiu Hsu , Chung-Chi Hu
Several geminiviruses have been show to possess cross-kingdom gene expression capability. In addition, the intergenic region (IR) of geminivirus genomes is known to regulate the transcription of viral early genes (complementary-sense, C-sense) and late genes (virion-sense, V-sense) located in opposite directions in viral genomic DNAs. However, the underlying mechanism remained elusive. In this study, the transcriptional regulation activities in the IR of ageratum yellow vein virus isolate NT (AYVV-NT), a monopartite geminivirus, were characterized in Escherichia coli, by using a promoter-trapping system. A functional bidirectional promoter core and regulatory elements for C- and V-sense genes were identified in the IR of AYVV-NT. Quantitative analyses revealed differences in promoter activity in various E. coli strains, suggesting that promoter regulation is strain-dependent and influenced by bacterial transcription factors. These findings provide insights into how plant-infecting geminiviruses may regulate gene expression in prokaryotic environments and highlight the potential applications of such viral regulatory elements in bacterial expression systems.
{"title":"Revelation of core promoter elements and bidirectional regulation of Geminivirus genes in Escherichia coli","authors":"Hsiao-En Lin , Ying-Wen Huang , Yi-Chin Lai , Na-Sheng Lin , Yau-Heiu Hsu , Chung-Chi Hu","doi":"10.1016/j.virusres.2026.199697","DOIUrl":"10.1016/j.virusres.2026.199697","url":null,"abstract":"<div><div>Several geminiviruses have been show to possess cross-kingdom gene expression capability. In addition, the intergenic region (IR) of geminivirus genomes is known to regulate the transcription of viral early genes (complementary-sense, C-sense) and late genes (virion-sense, V-sense) located in opposite directions in viral genomic DNAs. However, the underlying mechanism remained elusive. In this study, the transcriptional regulation activities in the IR of ageratum yellow vein virus isolate NT (AYVV-NT), a monopartite geminivirus, were characterized in <em>Escherichia coli</em>, by using a promoter-trapping system. A functional bidirectional promoter core and regulatory elements for C- and V-sense genes were identified in the IR of AYVV-NT. Quantitative analyses revealed differences in promoter activity in various <em>E. coli</em> strains, suggesting that promoter regulation is strain-dependent and influenced by bacterial transcription factors. These findings provide insights into how plant-infecting geminiviruses may regulate gene expression in prokaryotic environments and highlight the potential applications of such viral regulatory elements in bacterial expression systems.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"365 ","pages":"Article 199697"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}