{"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":"https://doi.org/10.1016/j.virol.2025.110391","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110391"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-01-02DOI: 10.1016/j.virol.2024.110388
Maryam Khalilzadeh, Dirk Jacobus Aldrich, Hans Jacob Maree, Amit Levy
{"title":"Complex interplay: The interactions between citrus tristeza virus and its host.","authors":"Maryam Khalilzadeh, Dirk Jacobus Aldrich, Hans Jacob Maree, Amit Levy","doi":"10.1016/j.virol.2024.110388","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110388","url":null,"abstract":"<p><p>Citrus tristeza virus (CTV) is one of the largest and most economically important RNA viruses infecting plants. CTV's interactions with various citrus hosts can result in three diseases: quick decline, stem pitting, or seedling yellows. Studying CTV poses several challenges owing to its significant genetic diversity and the highly specific occurrence of disease symptoms when different genotypes infect different citrus hosts. Considerable progress has been made to functionally characterize the virus-host interactions involved in the induction of CTV's three diseases, revealing that the four CTV ORFs (p33, p18, p13 and p23) play significant roles in determining the pathogenicity of CTV infections. These ORFs are unique to CTV and are not conserved among other members of the family Closteroviridae. This minireview aims to capture the complexity of the factors that have been shown to be involved in CTV disease induction and highlights recent work that provides novel insights into this pathosystem.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110388"},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-01-01Epub Date: 2024-11-28DOI: 10.1016/j.virol.2024.110324
Hui Fu, Dongli Pan
{"title":"Mechanisms of HSV gene regulation during latency and reactivation.","authors":"Hui Fu, Dongli Pan","doi":"10.1016/j.virol.2024.110324","DOIUrl":"10.1016/j.virol.2024.110324","url":null,"abstract":"<p><p>Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are prevalent human pathogens associated with many diseases. After productive (lytic) infection in peripheral tissues, HSV establishes lifelong latent infection in neurons of the peripheral nervous system. Periodic reactivation from latency, triggered by certain stimuli, can resume the lytic cycle. Lytic infection, latent infection and reactivation follow distinct viral gene expression patterns. The switch between the different infection programs is controlled by complicated regulatory mechanisms involving numerous viral and host molecules. Recent studies integrating cutting-edge technologies including neuronal culture techniques have greatly improved our understanding of the molecular details of latency and reactivation but many questions remain. This review summarizes the current knowledge about how HSV gene expression is regulated during latency and reactivation and discusses the important questions remaining to be addressed in future.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"602 ","pages":"110324"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a monoclonal antibody specifically recognizing a linear epitope on the E1 protein of Getah virus.","authors":"Muyang Liu, Tongwei Ren, Liping Zhang, Peijie Li, Zhen Zhong, Lingshan Zhou, Yifeng Qin, Kang Ouyang, Ying Chen, Weijian Huang, Zuzhang Wei","doi":"10.1016/j.virol.2024.110315","DOIUrl":"10.1016/j.virol.2024.110315","url":null,"abstract":"<p><p>Getah virus (GETV) is a mosquito-borne alphavirus that can cause disease outbreaks in domesticated mammals. The E1 protein of GETV plays a crucial role in mediating the fusion of viruses and host cells. In this study, the recombinant GETV E1 protein was expressed and administered to BALB/c mice. Hybridoma cells secreting a monoclonal antibody (mAb) 7D4-2 against E1 protein were subsequently obtained using a cell fusion protocol between SP2/0 cells and splenocytes. The reactivity of mAb 7D4-2 with GETV was confirmed through Western blot analysis and indirect immunofluorescence assay (IFA). A precise B cell linear epitope, 281-DIPDTAF-287, was identified using Western blot analysis with the produced mAb 7D4-2 by constructing and expressing a series of truncated His-fused E1 proteins. Conservation analysis indicated that this epitope is highly conserved in Group III strains of GETV, but exhibits an amino acid difference (T285S) compared to Group I, Group II, and Group IV. Cross-reactivity analysis by Western blot demonstrated that the B-cell epitope containing the mutation could be recognized by mAb 7D4-2. The ability of mAb 7D4-2 to recognize the epitope carrying the T285S mutation was further confirmed using an infectious clone of GETV. This study enhances the understanding of the biological characteristics of the E1 protein and will facilitate the future development of diagnostic tests for GETV.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"602 ","pages":"110315"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rapid test for hepatitis B core-related antigen to identify people living with hepatitis B having high viral load in Cameroon.","authors":"Richard Njouom, Alassane Ndiaye, Abdou Fatawou Modiyinji, Frederic Lissock, Jeanne Perpétue Vincent, Masaya Baba, Naoki Yamamoto, Atsushi Kaneko, Katsumi Aoyagi, Naofumi Hashimoto, Mari Nagai, Masato Ichikawa, Tetsuo Miura, Wataru Sugiura, Yasuhito Tanaka, Yusuke Shimakawa","doi":"10.1016/j.virol.2024.110316","DOIUrl":"10.1016/j.virol.2024.110316","url":null,"abstract":"<p><p>This study presents a retrospective assessment of the diagnostic performance of the newly developed hepatitis B core-related antigen rapid diagnostic test (HBcrAg-RDT) in detecting plasma samples with elevated hepatitis B virus (HBV) DNA levels (≥200,000 IU/ml) in Yaoundé, Cameroon. Samples were collected consecutively from treatment-naïve adults living with HBV between January 1, 2021, and June 30, 2023. Analyzing 146 samples from participants with a median age of 36 years, the HBcrAg-RDT exhibited a sensitivity of 97.5% (95% CI: 86.8-99.9) and a specificity of 77.4% (68.2-84.9) when compared to real-time PCR as the reference standard. These findings suggest that HBcrAg-RDT holds promise as a valuable point-of-care tool for diagnosing high HBV DNA levels, particularly in resource-limited settings. Further research will refine its practicality and effectiveness.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"602 ","pages":"110316"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-01-01Epub Date: 2024-11-29DOI: 10.1016/j.virol.2024.110311
Zihan Tian, Hao Wu, Rong Xu, Lun Yao, Wentao Li, Qigai He
{"title":"Development of a Duplex-ddPCR assay for accurate quantification of pseudorabies virus through systematic optimization of amplification bias.","authors":"Zihan Tian, Hao Wu, Rong Xu, Lun Yao, Wentao Li, Qigai He","doi":"10.1016/j.virol.2024.110311","DOIUrl":"10.1016/j.virol.2024.110311","url":null,"abstract":"<p><p>Pseudorabies (PR), caused by the pseudorabies virus (PRV), is highly contagious. Although qPCR is widely used for viral DNA detection, it struggles with low-level DNA identification and precise quantification. To address these issues, droplet digital PCR (ddPCR) has emerged as a more advanced method for detecting pathogens and providing absolute quantification of nucleic acids. The study introduces a ddPCR assay for accurate PRV quantification, addressing the challenges posed by the high GC content of the PRV genome. By optimizing factors such as primer and probe concentrations, annealing conditions, denaturation time, and cycle number, the assay overcomes limitations of traditional PCR techniques. The optimized ddPCR assay showed a wide linear dynamic range, with well-defined limits of blank (LOB) and detection (LOD). Testing confirmed the method's reproducibility, demonstrating its stability and reliability. This study provides key insights into optimizing ddPCR for GC-rich templates and serves as a useful reference for future experiments.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"602 ","pages":"110311"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-01-01Epub Date: 2024-12-03DOI: 10.1016/j.virol.2024.110298
Wenwen Hu, Deyuan Tang, Zhiyong Zeng, Bin Wang, Min Zhou, Yinming Mao, Piao Zhou, Song He
{"title":"Research progress on the molecular mechanism of immune escape of porcine reproductive and respiratory syndrome virus.","authors":"Wenwen Hu, Deyuan Tang, Zhiyong Zeng, Bin Wang, Min Zhou, Yinming Mao, Piao Zhou, Song He","doi":"10.1016/j.virol.2024.110298","DOIUrl":"10.1016/j.virol.2024.110298","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome (PRRS), caused by the porcine reproductive and respiratory syndrome virus (PRRSV), is a severe and highly contagious disease that results in significant economic losses for the pig industry. Currently, vaccination is one of the most effective methods for controlling PRRS; however, due to the extensive genetic variation of PRRSV and the generation of homologous immunity, vaccines provide protective effects only against homologous strains and lack effective cross-protection against heterologous strains. Furthermore, PRRSV encodes a variety of proteins with immune escape functions, and the mechanisms underlying these functions are complex and not yet fully understood. This complexity presents substantial challenges to the prevention, control, and eradication of the disease. Therefore, this article reviews the various escape mechanisms of PRRSV identified in recent years, with the aim of providing insights into the pathogenic mechanisms of PRRSV and facilitating the development of safer and more effective vaccines and therapeutics.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"602 ","pages":"110298"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2024-12-31DOI: 10.1016/j.virol.2024.110385
Hayato Harima, Yongjin Qiu, Michihito Sasaki, Joseph Ndebe, Kapila Penjaninge, Edgar Simulundu, Masahiro Kajihara, Aiko Ohnuma, Keita Matsuno, Naganori Nao, Yasuko Orba, Ayato Takada, Kanako Ishihara, William W Hall, Bernard M Hang'ombe, Hirofumi Sawa
{"title":"First identification and whole genome characterization of rotavirus C in pigs in Zambia.","authors":"Hayato Harima, Yongjin Qiu, Michihito Sasaki, Joseph Ndebe, Kapila Penjaninge, Edgar Simulundu, Masahiro Kajihara, Aiko Ohnuma, Keita Matsuno, Naganori Nao, Yasuko Orba, Ayato Takada, Kanako Ishihara, William W Hall, Bernard M Hang'ombe, Hirofumi Sawa","doi":"10.1016/j.virol.2024.110385","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110385","url":null,"abstract":"<p><p>Rotavirus C (RVC) causes acute gastroenteritis in neonatal piglets. Despite the clinical importance of RVC infection, the distribution and prevalence in pig populations in most African countries remains unknown. In this study, we identified RVC in Zambian pigs by metagenomic analysis. The full genome sequence of the RVC revealed two different VP4 sequences, implying that two different RVC strains (ZP18-77-c1 and ZP18-77-c2) were present in the same sample. Genetic analyses demonstrated that all segments of ZP18-77-c1 and ZP18-77-c2 showed high nucleotide sequence identities (87.7-94.5%) to known porcine RVC strains, and ZP18-77-c1 and ZP18-77-c2 strains were assigned to genotype constellations, G1-P[4]/P[14]-I13-R5-C5-M1-A7-N9-T10-E5-H1. We further screened RVC genomes among pig feces collected in Zambia (n = 147) by RT-qPCR, and 78 samples (53.1%) were positive. This study demonstrated the first full genome sequence of African RVC strains with a relatively high prevalence of RVC infection in the pig populations in Zambia.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110385"},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2024-12-31DOI: 10.1016/j.virol.2024.110387
Iain M Morgan
{"title":"The functions of papillomavirus E2 proteins.","authors":"Iain M Morgan","doi":"10.1016/j.virol.2024.110387","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110387","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110387"},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2024-12-31DOI: 10.1016/j.virol.2024.110384
Kyle W Shifflett, Dirk P Dittmer
{"title":"Mouse models of Kaposi sarcoma-associated herpesvirus (KSHV).","authors":"Kyle W Shifflett, Dirk P Dittmer","doi":"10.1016/j.virol.2024.110384","DOIUrl":"10.1016/j.virol.2024.110384","url":null,"abstract":"<p><p>Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is a prerequisite for the development of several human cancers, including Kaposi sarcoma and primary effusion lymphoma. Efficient long-term infection with KSHV and subsequent virally induced cell transformation is limited to humans, resulting in a lack of small animal models for KSHV-driven malignancies. Various attempts to create a mouse model for KSHV include infection of humanized mice, generating transgenic mice that ectopically express viral proteins, and grafting KSHV-infected tumor, primary, or immortalized cells onto immunodeficient mice. While no single mouse model can recapitulate the full range of KSHV-associated pathologies described in humans, each model adds an essential piece to the complete picture of KSHV infection and oncogenesis.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110384"},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}