Pub Date : 2025-02-01DOI: 10.1016/j.virol.2024.110387
Iain M. Morgan
All papillomaviruses encode an E2 protein and it is essential for the viral life cycle. E2 has three domains; a carboxyl-terminal DNA binding and dimerization domain, an amino-terminal protein interaction domain and a hinge region linking these two. Following homo-dimerization human papillomavirus E2 binds to four 12bp palindromic DNA sequences located in the non-coding long control region (LCR) of the viral genome. E2 has three main roles during the viral life cycle. It regulates transcription from the host, and potentially the viral, genome. It initiates viral replication via recruitment of the helicase E1 to the origin of replication. It segregates the viral genome during mitosis to ensure that viral genomes reside in daughter nuclei. This review will describe all of these functions and the mechanisms and interacting partners E2 uses to achieve them. It will also describe a potential role for E2 in mediating HPV cancer therapeutic outcomes.
{"title":"The functions of papillomavirus E2 proteins","authors":"Iain M. Morgan","doi":"10.1016/j.virol.2024.110387","DOIUrl":"10.1016/j.virol.2024.110387","url":null,"abstract":"<div><div>All papillomaviruses encode an E2 protein and it is essential for the viral life cycle. E2 has three domains; a carboxyl-terminal DNA binding and dimerization domain, an amino-terminal protein interaction domain and a hinge region linking these two. Following homo-dimerization human papillomavirus E2 binds to four 12bp palindromic DNA sequences located in the non-coding long control region (LCR) of the viral genome. E2 has three main roles during the viral life cycle. It regulates transcription from the host, and potentially the viral, genome. It initiates viral replication via recruitment of the helicase E1 to the origin of replication. It segregates the viral genome during mitosis to ensure that viral genomes reside in daughter nuclei. This review will describe all of these functions and the mechanisms and interacting partners E2 uses to achieve them. It will also describe a potential role for E2 in mediating HPV cancer therapeutic outcomes.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110387"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019331","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}
Pub Date : 2025-02-01DOI: 10.1016/j.virol.2025.110395
Jonathan L. Miller, Stefan Niewiesk
Respiratory syncytial virus (RSV) infections in elderly individuals are associated with increased rates of severe clinical disease and mortality compared to younger adults. Age-associated declines in numerous innate and adaptive immune parameters during RSV infection contribute to infection susceptibility, impaired viral clearance, and distorted cytokine profiles in the elderly. Impaired immune responses in this age group also adversely affect longevity of RSV immunity following vaccination in experimental settings. This review summarizes the effects of aging on cellular immune responses to RSV in humans and animal models, molecular mechanisms for these impaired responses where they have been elucidated, and the clinical consequences of impaired immunity in the elderly.
{"title":"Review of impaired immune parameters in RSV infections in the elderly","authors":"Jonathan L. Miller, Stefan Niewiesk","doi":"10.1016/j.virol.2025.110395","DOIUrl":"10.1016/j.virol.2025.110395","url":null,"abstract":"<div><div>Respiratory syncytial virus (RSV) infections in elderly individuals are associated with increased rates of severe clinical disease and mortality compared to younger adults. Age-associated declines in numerous innate and adaptive immune parameters during RSV infection contribute to infection susceptibility, impaired viral clearance, and distorted cytokine profiles in the elderly. Impaired immune responses in this age group also adversely affect longevity of RSV immunity following vaccination in experimental settings. This review summarizes the effects of aging on cellular immune responses to RSV in humans and animal models, molecular mechanisms for these impaired responses where they have been elucidated, and the clinical consequences of impaired immunity in the elderly.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110395"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019338","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}
Pub Date : 2025-02-01DOI: 10.1016/j.virol.2024.110341
Yunus Yukselten, Edidiong Akang, Lingyun Wang, PeiYi Su, Richard E. Sutton
HIV is still a pandemic; antiretroviral therapeutics for preventing and treating HIV infection continue to present significant challenges. The demand for new drugs and effective treatments remains ongoing. Here, we investigated the effects of combining Temsavir with other HIV entry inhibitors, including CD4 mimetic BNM-III-170, T20 or enfuvirtide, Ibalizumab, and Maraviroc. Our results show that TMR demonstrates both synergistic and antagonistic activity when combined those other entry inhibitors, depending on the concentration and the specific envelope used. Results suggest that while low-dose combinations, especially using Temsavir and CD4 mimetic, exhibited antagonistic effects, Temsavir showed synergy at low and medium concentrations in combination with enfuvirtide, Ibalizumab, and Maraviroc. These results are promising for the potential of co-administrating antiretrovirals for HIV treatment and highlights the importance of developing advanced antiviral strategies. On the other hand, the variable responses against different R5-tropic envelopes underscore the complexity of designing universally effective combination antiviral therapies.
{"title":"Investigating the combination of Temsavir and entry inhibitors on HIV replication: Synergistic and antagonistic effects observed against various R5-tropic envelopes","authors":"Yunus Yukselten, Edidiong Akang, Lingyun Wang, PeiYi Su, Richard E. Sutton","doi":"10.1016/j.virol.2024.110341","DOIUrl":"10.1016/j.virol.2024.110341","url":null,"abstract":"<div><div>HIV is still a pandemic; antiretroviral therapeutics for preventing and treating HIV infection continue to present significant challenges. The demand for new drugs and effective treatments remains ongoing. Here, we investigated the effects of combining Temsavir with other HIV entry inhibitors, including CD4 mimetic BNM-III-170, T20 or enfuvirtide, Ibalizumab, and Maraviroc. Our results show that TMR demonstrates both synergistic and antagonistic activity when combined those other entry inhibitors, depending on the concentration and the specific envelope used. Results suggest that while low-dose combinations, especially using Temsavir and CD4 mimetic, exhibited antagonistic effects, Temsavir showed synergy at low and medium concentrations in combination with enfuvirtide, Ibalizumab, and Maraviroc. These results are promising for the potential of co-administrating antiretrovirals for HIV treatment and highlights the importance of developing advanced antiviral strategies. On the other hand, the variable responses against different R5-tropic envelopes underscore the complexity of designing universally effective combination antiviral therapies.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110341"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793106","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}
Pub Date : 2025-02-01DOI: 10.1016/j.virol.2024.110368
Nadejda Beliakova-Bethell
Persistent HIV reservoir with different levels of proviral transcriptional activity represents a hurdle to HIV cure. The absence of a specific molecular signature or a “biomarker” to define cells latently infected with HIV limits reservoir eradication efforts. Biomarkers proposed in the literature define subsets of latently infected cells. This article discusses factors contributing to biomarker heterogeneity: external stimuli the cells are exposed to, tissue microenvironments, and person-to-person variation. Despite reservoir heterogeneity, several biomarkers, e.g., programmed cell death 1 and the Fc fragment of IgG low affinity IIa receptor, were reported consistently in multiple studies; however, they alone are unlikely to define all the HIV reservoir cells. Identifying a minimal set of cell surface proteins that together define all reservoir subsets is needed. Future studies will need to focus on the identification of co-expressed proteins that define the same sets of cells to reduce the number of proteins in a biomarker panel. A detailed characterization of tissue biomarkers and proteins expressed in latently infected cells of the myeloid lineage is needed to ensure that all the reservoirs are targeted throughout the body. Furthermore, the effect of underlying conditions that develop as people with HIV age on the manifestation of latency should be evaluated. With the development of novel technologies, such as spatial transcriptomics and proteomics, such endeavors will soon be possible. Thus, there is promise that a minimal set of proteins defining all the different reservoir subsets can be identified and developed into a reservoir targeting strategy.
{"title":"Eliminating the persistent HIV reservoir based on biomarker expression – How do we get there?","authors":"Nadejda Beliakova-Bethell","doi":"10.1016/j.virol.2024.110368","DOIUrl":"10.1016/j.virol.2024.110368","url":null,"abstract":"<div><div>Persistent HIV reservoir with different levels of proviral transcriptional activity represents a hurdle to HIV cure. The absence of a specific molecular signature or a “biomarker” to define cells latently infected with HIV limits reservoir eradication efforts. Biomarkers proposed in the literature define subsets of latently infected cells. This article discusses factors contributing to biomarker heterogeneity: external stimuli the cells are exposed to, tissue microenvironments, and person-to-person variation. Despite reservoir heterogeneity, several biomarkers, e.g., programmed cell death 1 and the Fc fragment of IgG low affinity IIa receptor, were reported consistently in multiple studies; however, they alone are unlikely to define all the HIV reservoir cells. Identifying a minimal set of cell surface proteins that together define all reservoir subsets is needed. Future studies will need to focus on the identification of co-expressed proteins that define the same sets of cells to reduce the number of proteins in a biomarker panel. A detailed characterization of tissue biomarkers and proteins expressed in latently infected cells of the myeloid lineage is needed to ensure that all the reservoirs are targeted throughout the body. Furthermore, the effect of underlying conditions that develop as people with HIV age on the manifestation of latency should be evaluated. With the development of novel technologies, such as spatial transcriptomics and proteomics, such endeavors will soon be possible. Thus, there is promise that a minimal set of proteins defining all the different reservoir subsets can be identified and developed into a reservoir targeting strategy.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110368"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901355","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}
Pub Date : 2025-02-01DOI: 10.1016/j.virol.2024.110361
Shu-yuan Guo , Wen-hai Feng
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a significant pathogen in the swine industry. MicroRNAs (miRNAs), a class of small non-coding RNA molecules, have risen to prominence as key regulators of gene expression at the post-transcriptional level. Their significance in regulating virus-host interactions is now widely acknowledged. So far, more than 30 miRNAs have been found to play a role in PRRSV infection. They can regulate viral genome stability and protein synthesis by targeting PRRSV RNA, and modulate the host immune response, thus affecting PRRSV replication. Understanding the role of miRNAs in PRRSV infection can further elucidate the pathogenesis of PRRSV and pave the way for the development of new antiviral strategies through miRNA-based therapies. This review will focus on how host miRNAs alter PRRSV infection, underscoring their multifaceted involvement in the interplay between virus and host.
{"title":"Host microRNAs as regulators of porcine reproductive and respiratory syndrome virus infection","authors":"Shu-yuan Guo , Wen-hai Feng","doi":"10.1016/j.virol.2024.110361","DOIUrl":"10.1016/j.virol.2024.110361","url":null,"abstract":"<div><div>Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a significant pathogen in the swine industry. MicroRNAs (miRNAs), a class of small non-coding RNA molecules, have risen to prominence as key regulators of gene expression at the post-transcriptional level. Their significance in regulating virus-host interactions is now widely acknowledged. So far, more than 30 miRNAs have been found to play a role in PRRSV infection. They can regulate viral genome stability and protein synthesis by targeting PRRSV RNA, and modulate the host immune response, thus affecting PRRSV replication. Understanding the role of miRNAs in PRRSV infection can further elucidate the pathogenesis of PRRSV and pave the way for the development of new antiviral strategies through miRNA-based therapies. This review will focus on how host miRNAs alter PRRSV infection, underscoring their multifaceted involvement in the interplay between virus and host.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110361"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901385","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}
Pub Date : 2025-02-01DOI: 10.1016/j.virol.2024.110386
Cade R. Rahlf, Vera L. Tarakanova
Decades of research have defined the function of interferon regulatory factors (IRFs) in the antiviral immune response. Interferon regulatory factor-1 (IRF-1) is the founding member of the IRF family, with recognized antiviral effects across diverse virus infections. While most antiviral activities of IRF-1 were defined in vitro, fewer studies examined the role of IRF-1 during viral infection of an intact host. Taking advantage of mouse models of global or cell type-specific IRF-1 deficiency, recent studies demonstrate intriguing virus- and cell type-specific functions of IRF-1 during in vivo infection, underlining the complexity of this ancient transcription factor. Here, we review the role of IRF-1 during acute and chronic viral infections of an intact host, with particular focus on relating observations found in mouse models to those observed in a recent study of pediatric patients with IRF-1 insufficiency. By appreciating the complexity of IRF-1 in the immune response, we highlight several virus- and cell type-specific functions of IRF-1 in contributing to host antiviral immunity.
{"title":"Role of Interferon Regulatory Factor 1 in acute and chronic virus infections","authors":"Cade R. Rahlf, Vera L. Tarakanova","doi":"10.1016/j.virol.2024.110386","DOIUrl":"10.1016/j.virol.2024.110386","url":null,"abstract":"<div><div>Decades of research have defined the function of interferon regulatory factors (IRFs) in the antiviral immune response. Interferon regulatory factor-1 (IRF-1) is the founding member of the IRF family, with recognized antiviral effects across diverse virus infections. While most antiviral activities of IRF-1 were defined <em>in vitro</em>, fewer studies examined the role of IRF-1 during viral infection of an intact host. Taking advantage of mouse models of global or cell type-specific IRF-1 deficiency, recent studies demonstrate intriguing virus- and cell type-specific functions of IRF-1 during <em>in vivo</em> infection, underlining the complexity of this ancient transcription factor. Here, we review the role of IRF-1 during acute and chronic viral infections of an intact host, with particular focus on relating observations found in mouse models to those observed in a recent study of pediatric patients with IRF-1 insufficiency. By appreciating the complexity of IRF-1 in the immune response, we highlight several virus- and cell type-specific functions of IRF-1 in contributing to host antiviral immunity.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110386"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928884","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}
Pub Date : 2025-02-01DOI: 10.1016/j.virol.2024.110334
Shaokang Yang , Xiaotong Yang , Weiyan Zhu, Chongda Luo, Xintong Yan, Wei Li, Ruiyuan Cao, Wu Zhong
Zika virus (ZIKV) is a mosquito-borne, positive-stranded RNA virus, ZIKV infection during pregnancy threatens pregnancy and fetal health, and it remains a global health threat, there are no clinically approved vaccines or antiviral drugs for the treatment of ZIKV infection. VV116 is an oral drug candidate of nucleoside analog against SARS-CoV-2 that has demonstrated a satisfactory safety and tolerability in healthy subjects. Our study shows for the first time that VV116 has potent activity against ZIKV. We verified that VV116 can inhibit the RNA and protein level of ZIKV in vitro. Importantly, treatment with VV116 significantly enhanced survival and provided protection in ZIKV-infected ICR mice. VV116 acted at the replication stage of viral infection cycle, and exhibited reasonable inhibition of ZIKV replicons. Collectively, the in vitro and in vivo anti-ZIKV activity of VV116 suggests that it is a promising anti-ZIKV drug candidate.
{"title":"The novel COVID-19 treatment VV116 is a potential inhibitor of Zika virus","authors":"Shaokang Yang , Xiaotong Yang , Weiyan Zhu, Chongda Luo, Xintong Yan, Wei Li, Ruiyuan Cao, Wu Zhong","doi":"10.1016/j.virol.2024.110334","DOIUrl":"10.1016/j.virol.2024.110334","url":null,"abstract":"<div><div>Zika virus (ZIKV) is a mosquito-borne, positive-stranded RNA virus, ZIKV infection during pregnancy threatens pregnancy and fetal health, and it remains a global health threat, there are no clinically approved vaccines or antiviral drugs for the treatment of ZIKV infection. VV116 is an oral drug candidate of nucleoside analog against SARS-CoV-2 that has demonstrated a satisfactory safety and tolerability in healthy subjects. Our study shows for the first time that VV116 has potent activity against ZIKV. We verified that VV116 can inhibit the RNA and protein level of ZIKV <em>in vitro</em>. Importantly, treatment with VV116 significantly enhanced survival and provided protection in ZIKV-infected ICR mice. VV116 acted at the replication stage of viral infection cycle, and exhibited reasonable inhibition of ZIKV replicons. Collectively, the <em>in vitro</em> and <em>in vivo</em> anti-ZIKV activity of VV116 suggests that it is a promising anti-ZIKV drug candidate.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110334"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796752","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}
Pub Date : 2025-02-01DOI: 10.1016/j.virol.2024.110381
Diego A. Olivo , Simona Kraberger , Elliott S. Chiu , Joy M. Custer , Danny Jackson , Melanie Regney , Michael C. Lund , Rohan A. Bandoo , Victor Aguiar de Souza Penha , Dean Drake , Kevin J. McGraw , Arvind Varsani
North America is home to over 40 species of migratory waterfowl. Utilizing tissue and cloacal-swab sampling from hunter-harvested carcasses in 2021–2023, we identified circular DNA viruses associated with 116 waterfowl samples from nine species (American wigeons, Mexican ducks, northern shovelers, northern pintails, canvasbacks, mallards, American black ducks, gadwalls, and green-winged teals). We determined the genome sequences of viruses in the families Circoviridae (n = 18) and Hepadnaviridae (n = 2) from the 13 virus-infected birds. The 18 circoviruses can be classified into four circovirus lineages: duck circovirus, wigfec circovirus 1, and two new lineages, marcaroli circovirus and spata circovirus. The new circovirus lineages identified are most closely related to waterfowl circoviruses based on the pairwise identities and phylogenetic analyses of full genomes, replication-associated protein, and capsid protein sequences. The two identified hepadnavirus genomes are part of the duck hepatitis B virus lineage sharing >89% identity with known ones.
{"title":"Avian circoviruses and hepadnaviruses identified in tissue samples of various waterfowl","authors":"Diego A. Olivo , Simona Kraberger , Elliott S. Chiu , Joy M. Custer , Danny Jackson , Melanie Regney , Michael C. Lund , Rohan A. Bandoo , Victor Aguiar de Souza Penha , Dean Drake , Kevin J. McGraw , Arvind Varsani","doi":"10.1016/j.virol.2024.110381","DOIUrl":"10.1016/j.virol.2024.110381","url":null,"abstract":"<div><div>North America is home to over 40 species of migratory waterfowl. Utilizing tissue and cloacal-swab sampling from hunter-harvested carcasses in 2021–2023, we identified circular DNA viruses associated with 116 waterfowl samples from nine species (American wigeons, Mexican ducks, northern shovelers, northern pintails, canvasbacks, mallards, American black ducks, gadwalls, and green-winged teals). We determined the genome sequences of viruses in the families <em>Circoviridae</em> (n = 18) and <em>Hepadnaviridae</em> (n = 2) from the 13 virus-infected birds. The 18 circoviruses can be classified into four circovirus lineages: duck circovirus, wigfec circovirus 1, and two new lineages, marcaroli circovirus and spata circovirus. The new circovirus lineages identified are most closely related to waterfowl circoviruses based on the pairwise identities and phylogenetic analyses of full genomes, replication-associated protein, and capsid protein sequences. The two identified hepadnavirus genomes are part of the duck hepatitis B virus lineage sharing >89% identity with known ones.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110381"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916764","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}
Pub Date : 2025-02-01DOI: 10.1016/j.virol.2024.110352
Hongqiang Zhang , Fangping Wang , Haotai Chen , Shasha Wang , Lina Tong , Huibao Wang , Jiangfeng Fan , Xiangping Yin , Xiangwei Wang , Yuefeng Sun , Xiaolong Gao , Shanhui Ren
Capripoxviruses (CaPVs), such as lumpy skin disease, sheep pox, and goat pox, cause significant production and economic losses and are major constraints to the growth of livestock production in endemic areas. Understanding the pathogenic mechanism of CaPVs and their translation into clinical applications depends on the availability of a suitable cell line. In this study, we used a lentiviral packaging system to establish an immortalized hTERT-bOEC cell line by ectopic introduction of human telomerase reverse transcriptase (hTERT). Western blotting, indirect immunofluorescence, and flow cytometry analyses revealed that hTERT was successfully integrated into the genome of hTERT-bOEC cells. Crucially, this hTERT-bOEC cell line was highly susceptible to LSDV, SPPV, and GTPV infections. Establishing hTERT-bOECs is critical for basic research, clinical application, and vaccine development related to CaPVs. Furthermore, RNA-seq analyses revealed a similar differential expression of genes and enrichment of signaling pathways to CaPV infections in hTERT-bOECs. Real-time quantitative qPCR further confirmed the top five up-regulated and down-regulated differentially expressed genes among the CaPV infections. Transcriptome analyses provide deep insight into the biological characteristics of the replication process in CaPV infections.
{"title":"Comparative RNA sequencing analysis of three Capripoxvirus infections in an immortalized hTERT-bOEC cell model","authors":"Hongqiang Zhang , Fangping Wang , Haotai Chen , Shasha Wang , Lina Tong , Huibao Wang , Jiangfeng Fan , Xiangping Yin , Xiangwei Wang , Yuefeng Sun , Xiaolong Gao , Shanhui Ren","doi":"10.1016/j.virol.2024.110352","DOIUrl":"10.1016/j.virol.2024.110352","url":null,"abstract":"<div><div>Capripoxviruses (CaPVs), such as lumpy skin disease, sheep pox, and goat pox, cause significant production and economic losses and are major constraints to the growth of livestock production in endemic areas. Understanding the pathogenic mechanism of CaPVs and their translation into clinical applications depends on the availability of a suitable cell line. In this study, we used a lentiviral packaging system to establish an immortalized hTERT-bOEC cell line by ectopic introduction of human telomerase reverse transcriptase (hTERT). Western blotting, indirect immunofluorescence, and flow cytometry analyses revealed that hTERT was successfully integrated into the genome of hTERT-bOEC cells. Crucially, this hTERT-bOEC cell line was highly susceptible to LSDV, SPPV, and GTPV infections. Establishing hTERT-bOECs is critical for basic research, clinical application, and vaccine development related to CaPVs. Furthermore, RNA-seq analyses revealed a similar differential expression of genes and enrichment of signaling pathways to CaPV infections in hTERT-bOECs. Real-time quantitative qPCR further confirmed the top five up-regulated and down-regulated differentially expressed genes among the CaPV infections. Transcriptome analyses provide deep insight into the biological characteristics of the replication process in CaPV infections.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110352"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866955","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}
Pub Date : 2025-02-01DOI: 10.1016/j.virol.2025.110391
Shraddha Y. Gaikwad , Ashwini More , Chandrabhan Seniya , Kunal Verma , Madhuri Chandane-Tak , Vijay Nema , Shobhit Kumar , Anupam Mukherjee
The integration of nanotechnology into antiretroviral drug delivery systems presents a promising avenue to address challenges posed by long-term antiretroviral therapies (ARTs), including poor bioavailability, drug-induced toxicity, and resistance. These limitations impact the therapeutic effectiveness and quality of life for individuals living with HIV. Nanodrug delivery systems, particularly nanoemulsions, have demonstrated potential in improving drug solubility, enhancing bioavailability, and minimizing systemic toxicity. Moreover, nanodrug platforms can target viral reservoirs, potentially reducing the emergence of drug-resistant strains—a significant challenge in anti-HIV treatment. This study evaluates the biological efficacy of a rosemary oil-based nanoemulsion loaded with Nelfinavir (NFV) and Epigallocatechin Gallate (EGCG), which demonstrated HIV-1 suppression at sub-CC₅₀ concentrations across two distinct cellular systems. The synergistic interaction between NFV and EGCG was confirmed through cellular assays, enzymatic studies, and molecular interaction analysis. In vitro experiments revealed that the NE-NFV-EGCG nanoemulsion exhibited enhanced HIV-1 inhibitory activity compared to pure NFV, highlighting a promising therapeutic synergy. The findings suggest that EGCG could be a valuable adjunct in NFV-based regimens for HIV management. Molecular interaction studies further confirmed the nanoemulsion's inhibitory potential against the HIV-1 protease enzyme. This study marks a significant advancement in HIV-1 treatment by documenting, for the first time, the synergistic inhibitory activity of NFV and EGCG. The novel nanoformulation offers improved oral bioavailability, minimal side effects, and enhanced therapeutic outcomes. Future studies are needed to optimize the formulation for clinical applications, including sustained drug release and drug transport mechanisms.
{"title":"Synergistic inhibition of HIV-1 by Nelfinavir and Epigallocatechin Gallate: A novel nanoemulsion-based therapeutic approach","authors":"Shraddha Y. Gaikwad , Ashwini More , Chandrabhan Seniya , Kunal Verma , Madhuri Chandane-Tak , Vijay Nema , Shobhit Kumar , Anupam Mukherjee","doi":"10.1016/j.virol.2025.110391","DOIUrl":"10.1016/j.virol.2025.110391","url":null,"abstract":"<div><div>The integration of nanotechnology into antiretroviral drug delivery systems presents a promising avenue to address challenges posed by long-term antiretroviral therapies (ARTs), including poor bioavailability, drug-induced toxicity, and resistance. These limitations impact the therapeutic effectiveness and quality of life for individuals living with HIV. Nanodrug delivery systems, particularly nanoemulsions, have demonstrated potential in improving drug solubility, enhancing bioavailability, and minimizing systemic toxicity. Moreover, nanodrug platforms can target viral reservoirs, potentially reducing the emergence of drug-resistant strains—a significant challenge in anti-HIV treatment. This study evaluates the biological efficacy of a rosemary oil-based nanoemulsion loaded with Nelfinavir (NFV) and Epigallocatechin Gallate (EGCG), which demonstrated HIV-1 suppression at sub-CC₅₀ concentrations across two distinct cellular systems. The synergistic interaction between NFV and EGCG was confirmed through cellular assays, enzymatic studies, and molecular interaction analysis. In vitro experiments revealed that the NE-NFV-EGCG nanoemulsion exhibited enhanced HIV-1 inhibitory activity compared to pure NFV, highlighting a promising therapeutic synergy. The findings suggest that EGCG could be a valuable adjunct in NFV-based regimens for HIV management. Molecular interaction studies further confirmed the nanoemulsion's inhibitory potential against the HIV-1 protease enzyme. This study marks a significant advancement in HIV-1 treatment by documenting, for the first time, the synergistic inhibitory activity of NFV and EGCG. The novel nanoformulation offers improved oral bioavailability, minimal side effects, and enhanced therapeutic outcomes. Future studies are needed to optimize the formulation for clinical applications, including sustained drug release and drug transport mechanisms.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110391"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960908","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}
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