Cecilia Di Genova, Caroline J Warren, Simon Johnson, Sofia Riccio, Kelly Roper, Saumya S Thomas, Audra-Lynne Schlachter, David Jorge, Kajal Ralh, Jafar Hassan, Elizabeth Billington, Alejandro Nunez, Ian H Brown, Marek J Slomka, Ashley C Banyard, Joe James
{"title":"Pigeons exhibit low susceptibility and poor transmission capacity for H5N1 clade 2.3.4.4b high pathogenicity avian influenza virus.","authors":"Cecilia Di Genova, Caroline J Warren, Simon Johnson, Sofia Riccio, Kelly Roper, Saumya S Thomas, Audra-Lynne Schlachter, David Jorge, Kajal Ralh, Jafar Hassan, Elizabeth Billington, Alejandro Nunez, Ian H Brown, Marek J Slomka, Ashley C Banyard, Joe James","doi":"10.1099/jgv.0.002156","DOIUrl":"10.1099/jgv.0.002156","url":null,"abstract":"<p><p>The ongoing panzootic of H5N1 high pathogenicity avian influenza virus (HPAIV) has caused the deaths of over half a billion wild birds and poultry and has led to spillover events in both wild and domestic mammals, alongside sporadic human infections. A key driver of this panzootic is the apparent high viral fitness across diverse avian species, which facilitates an increased interface between wild and domestic species. <i>Columbiformes</i> (pigeons and doves) are commonly found on poultry premises, yet little is known about their potential role in contemporary HPAIV disease ecology. Here, we investigated the epidemiological role of pigeons (<i>Columba livia</i>) by determining their susceptibility using decreasing doses of clade 2.3.4.4b H5N1 HPAIV (genotype AB). We investigated infection outcomes and transmission potential between pigeons and chickens. Following direct inoculation, pigeons did not develop clinical signs, and only those inoculated with the highest dose shed viral RNA (vRNA) or seroconverted to H5N1-AB, revealing a 50% minimum infectious dose (MID) of 10<sup>5</sup> 50% egg infectious dose. Even in the high-dose group, only low-level shedding and environmental contamination were observed, and low-level viral RNAs were present in the tissues of directly inoculated pigeons, with no distinct pathological lesions. Pigeons did not transmit the virus to pigeons or chickens placed in direct contact. We observed distinct differences in sialic acid receptor distribution in the pigeon respiratory tract compared to chickens and ducks. Together, these findings suggest that pigeons have low susceptibility to clade 2.3.4.4b H5N1 HPAIV and are unlikely to contribute significantly to virus maintenance, transmission to poultry or zoonotic infection.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment of a Chikungunya virus pseudotype system strictly dependent on viral protein expression.","authors":"Atsushi Tanaka, Takayuki Miyazawa","doi":"10.1099/jgv.0.002138","DOIUrl":"10.1099/jgv.0.002138","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) is an enveloped RNA virus that causes Chikungunya fever in humans. It is classified as an arbovirus (arthropod-borne virus) and is transmitted by mosquitoes. Therefore, CHIKV can replicate in many types of cells derived from mammals or insects. In this study, we tried to establish the widely useable CHIKV pseudotype system, adapting various viral species, and we demonstrated the production of Chikungunya pseudotype virus bearing the envelope protein from two different viral families, <i>Coronaviridae</i> or <i>Rhabdoviridae</i>, i.e. severe acute respiratory syndrome coronavirus 2 spike protein or vesicular stomatitis virus glycoprotein, respectively. We found that the capsid protein of CHIKV is not always necessary in the formation of CHIKV-based pseudotypes, but that the capsid protein increases the efficiency of expression of the sub-genomic RNA which codes the labelled genes. Our established pseudotype virus-producing system supplied a sufficient titre of virions for application to most virological experiments that showed more than 10<sup>4</sup> focus-forming units per millilitre. The pseudotype infections were strictly dependent on compatibility between the viral envelope protein and its receptor, and there was no false-positive background infection. Our established pseudotype virus system can be used as a robust platform to study various virus infections and for screening and in-depth evaluation of neutralizing antibodies and antiviral agents.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 8","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aaron Mamane-Logsdon, Isabelle Zane, June See Chong, Oscar Hou In Chou, Jiajun Huang, Mahesh Rawal, Adam C Gillman, Wiyada Wongwiwat, Mostafa Saleban, I'ah Donovan-Banfield, David A Matthews, Robert E White
{"title":"A direct RNA-seq-based EBV latency transcriptome offers insights into the biogenesis of EBV gene products.","authors":"Aaron Mamane-Logsdon, Isabelle Zane, June See Chong, Oscar Hou In Chou, Jiajun Huang, Mahesh Rawal, Adam C Gillman, Wiyada Wongwiwat, Mostafa Saleban, I'ah Donovan-Banfield, David A Matthews, Robert E White","doi":"10.1099/jgv.0.002134","DOIUrl":"10.1099/jgv.0.002134","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) ubiquitously infects humans, establishing lifelong persistence in B cells. <i>In vitro</i>, EBV-infected B cells can establish a lymphoblastoid cell line (LCL). EBV's transcripts in LCLs (latency III) produce six nuclear proteins [EBV nuclear antigens (EBNAs)], two latency membrane proteins (LMPs) and various microRNAs and putative long non-coding RNAs [BamHI A rightward transcripts (BARTs)]. The BART and EBNA transcription units are characterized by extensive alternative splicing. We generated LCLs with B95-8 EBV-BACs, including one engineered with 'barcodes' in the first and last repeat of internal repeat 1 (IR1), and analysed their EBV transcriptomes using long-read nanopore direct RNA-seq. Our pipeline ensures appropriate mapping of the W promoter (Wp) 5' exon and corrects W1-W2 exon counts that misalign to IR1. This suggests that splicing across IR1 largely includes all W exons and that Wp-derived transcripts more frequently encode the EBNA-LP start codon than Cp transcripts. Analysis identified a short variant of exon W2 and a novel polyadenylation site before EBNA2, provided insights into BHRF1 miRNA processing and suggested co-ordination between polyadenylation and splice site usage, although improved read depth and integrity are required to confirm this. The BAC region disrupts the integrity of BART transcripts through premature polyadenylation and cryptic splice sites in the hygromycin expression cassette. Finally, a few transcripts extended across established gene boundaries, running from EBNA to BART to LMP2 gene regions, sometimes including novel exons between EBNA1 and the BART promoter. We have produced an EBV annotation based on these findings to help others better characterize EBV transcriptomes in the future.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 8","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanistic insights into Nipah virus 5' UTR functionality reveal an antiviral target.","authors":"Lishi Liu, Chaohu Pan, Zhen Chen, Fang Zhang, Wuxiang Guan, Aiping Zeng, Haojie Hao","doi":"10.1099/jgv.0.002141","DOIUrl":"https://doi.org/10.1099/jgv.0.002141","url":null,"abstract":"<p><p>The highly pathogenic Nipah virus (NiV), a World Health Organization priority pathogen with pandemic potential, remains a critical public health threat due to its capacity to cause fatal encephalitis and respiratory disease. Despite its 1998 emergence, no approved therapeutics exist against NiV infection, underscoring the urgent need to identify genomic regulatory elements as antiviral targets. Our study focuses on the extended 5' UTRs characteristic of NiV transcripts, a distinctive genomic feature whose functional significance remained enigmatic. Comparative reporter assays showed these UTRs strongly inhibit downstream ORF translation through mechanisms distinct from internal ribosome entry site activity. Mutagenesis studies identified upstream ATG elements in multiple transcripts as critical regulators of translational efficiency, with the C 5' UTR exhibiting maximal suppression. A functional hotspot spanning within the C 5' UTR was mapped as the primary ribosomal initiation blockade, and ribosome leaky scanning was confirmed as the mechanism enabling dual-protein expression. Notably, therapeutic targeting of this regulatory element with antisense oligonucleotides significantly impaired viral replication. These findings provide fundamental insights into henipaviral translation regulation while identifying concrete antiviral targets, particularly the druggable C 5' UTR element, advancing efforts to combat this biosafety level 4 pathogen.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 8","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sead Sabanadzovic, Chantal Abergel, Marı́a A Ayllón, Leticia Botella, Marta Canuti, Yuto Chiba, JeanMichel Claverie, Robert H A Coutts, Stefania Daghino, Livia Donaire, Marco Forgia, Ondřej Hejna, Jichun Jia, Daohong Jiang, Ioly Kotta-Loizou, Mart Krupovic, Andrew S Lang, Matthieu Legendre, Shin-Yi Lee Marzano, Fan Mu, Uri Neri, Luca Nerva, Judit Pénzes, Anna Poimala, Sofia Rigou, Yukiyo Sato, Wajeeha Shamsi, Suvi Sutela, Nobuhiro Suzuki, Massimo Turina, Syun-Ichi Urayama, Eeva J Vainio, Jiatao Xie, Ictv Taxonomy Summary Consortium
{"title":"Erratum: Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Fungal and Protist Viruses Subcommittee, 2025.","authors":"Sead Sabanadzovic, Chantal Abergel, Marı́a A Ayllón, Leticia Botella, Marta Canuti, Yuto Chiba, JeanMichel Claverie, Robert H A Coutts, Stefania Daghino, Livia Donaire, Marco Forgia, Ondřej Hejna, Jichun Jia, Daohong Jiang, Ioly Kotta-Loizou, Mart Krupovic, Andrew S Lang, Matthieu Legendre, Shin-Yi Lee Marzano, Fan Mu, Uri Neri, Luca Nerva, Judit Pénzes, Anna Poimala, Sofia Rigou, Yukiyo Sato, Wajeeha Shamsi, Suvi Sutela, Nobuhiro Suzuki, Massimo Turina, Syun-Ichi Urayama, Eeva J Vainio, Jiatao Xie, Ictv Taxonomy Summary Consortium","doi":"10.1099/jgv.0.002144","DOIUrl":"10.1099/jgv.0.002144","url":null,"abstract":"","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 8","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mart Krupovic, Diana P Baquero, Eduardo A Bignon, Ariane Bize, Guillaume Borrel, Mingwei Cai, Lanming Chen, Marion Coves, Changhai Duan, Simonetta Gribaldo, Eugene V Koonin, Meng Li, Lirui Liu, Yang Liu, Ying Liu, Sofia Medvedeva, Yimin Ni, Apoorva Prabhu, Christian Rinke, Yongjie Wang, Tianqi Xu, Shuling Yan, Qinglu Zeng, Rui Zhang, Ictv Taxonomy Summary Consortium
{"title":"Erratum: Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Archaeal Viruses Subcommittee, 2025.","authors":"Mart Krupovic, Diana P Baquero, Eduardo A Bignon, Ariane Bize, Guillaume Borrel, Mingwei Cai, Lanming Chen, Marion Coves, Changhai Duan, Simonetta Gribaldo, Eugene V Koonin, Meng Li, Lirui Liu, Yang Liu, Ying Liu, Sofia Medvedeva, Yimin Ni, Apoorva Prabhu, Christian Rinke, Yongjie Wang, Tianqi Xu, Shuling Yan, Qinglu Zeng, Rui Zhang, Ictv Taxonomy Summary Consortium","doi":"10.1099/jgv.0.002145","DOIUrl":"10.1099/jgv.0.002145","url":null,"abstract":"","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 8","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ulrike Breitinger, Zeina Ihab Seifeldin Zakaria, Haya Alaa Mahgoub, Anna-Lena Wiessler, Esra Tuerker, Carmen Villmann, Hans-Georg Breitinger
{"title":"Activity and cellular distribution of ORF3a mutants of SARS-CoV-2 variants of concern.","authors":"Ulrike Breitinger, Zeina Ihab Seifeldin Zakaria, Haya Alaa Mahgoub, Anna-Lena Wiessler, Esra Tuerker, Carmen Villmann, Hans-Georg Breitinger","doi":"10.1099/jgv.0.002135","DOIUrl":"10.1099/jgv.0.002135","url":null,"abstract":"<p><p>Infection with SARS-CoV-2 continues to be a threat to human health. Despite successful immunization campaigns, effective treatment of COVID-19 remains an essential need to help patients and prevent the spread of new virus strains. Viroporins are intracellular ion channels that are essential for virus replication and release, thus presenting promising pharmaceutical targets. Mutations found in variants of concern (VOC) are expected to increase the virulence of the new virus strains. Recognizing the effects of these mutations at the molecular level is essential for the development of improved therapies. Here, we characterized the putative viroporin ORF3a found in VOCs of SARS-CoV-2, using expression constructs containing a myc-tag for identification, and an optional membrane-directing signal peptide. Additionally, constructs containing N-terminal fluorescence protein tags were prepared. Expression and cell surface transport in HEK-293 cells were studied using Western blot and dot blot assays, and the cellular distribution of fluorescent-marked ORF3a was studied using subcellular organelle markers and high-resolution fluorescence microscopy. Viroporin activity of all ORF3a constructs was assessed using cell viability and metabolic assays, as well as patch-clamp recordings of recombinant ORF3a. All ORF3a mutants were expressed well in the recombinant system, and the presence of a signal peptide increased expression on the cellular surface. Intracellular distribution was similar for all variants. The VOC mutants ORF3a-S171L and ORF3a-Q57H showed reduced cytotoxic activity and sensitivity to the viroporin inhibitor rimantadine, respectively, suggesting these positions to be relevant for ORF3a function and a starting point for the search of novel antiviral drugs.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 8","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12328068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optimum level of NEDD4 and its interaction with nsP3 are crucial to facilitate efficient Chikungunya virus (CHIKV) infection.","authors":"Suchanda Verma, Sanchari Chatterjee, Supriya Suman Keshry, Ajit Kumar Dhal, Bijita Bhowmick, Janu Newar, Soma Chattopadhyay, Archana Ghatak","doi":"10.1099/jgv.0.002136","DOIUrl":"10.1099/jgv.0.002136","url":null,"abstract":"<p><p>Chikungunya is a febrile infection caused by the Chikungunya virus (CHIKV), an alphavirus which has emerged as a serious public health problem globally. Despite extensive research, our understanding of different host factors facilitating effective CHIKV infection is not clear yet. NEDD4, a member of the E3 ubiquitin ligase, is one such protein. Here, the importance of NEDD4 has been explored during CHIKV infection <i>in vitro</i>. It was observed that the level of NEDD4 is downregulated after CHIKV infection. Interestingly, the CHIKV-nsP3 level and the viral load were decreased significantly when NEDD4 was silenced, while a 93% decrease in the viral load was observed in the case of NEDD4 overexpression, indicating the importance of an optimum level of NEDD4 for effective CHIKV infection. Further study revealed that there was interaction between the NEDD4 and CHIKV-nsP3 proteins through co-immunoprecipitation (CO-IP) during CHIKV infection. Additionally, <i>in silico</i> data illustrated that the WW domain of NEDD4 can bind to the nsP3, as well as the macrodomain of nsP3 (nsp3-MD) of CHIKV. These data were further confirmed by the pull-down assay with purified nsP3-MD. The finding suggested that the host protein NEDD4 might interact directly with nsP3-MD during the CHIKV infection. However, the presence of a faint band of NEDD4 along with nsP3-MD in the pull-down assay may indicate the involvement of some other residues for this interaction. These <i>in silico</i> data were further confirmed by the CO-IP experiments, where all domains of nsP3, MD (macrodomain), AUD (alphavirus unique domain) and HVD (hypervariable domain) were found to interact with NEDD4. Additional experiments with a truncated form of MD, MD1 (1-100 residues of amino acid), revealed that this region is not able to maintain the interaction with NEDD4, indicating the crucial role of the C-terminal region of MD for this binding. In conclusion, these findings offer valuable insights about the importance of NEDD4 during CHIKV infection and the residues of nsP3 for its interaction, which might be useful to design future therapeutics against CHIKV.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 8","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victor Javier Cruz-Holguín, Ivonne Sagrario Romero-Flores, Luis Gerardo Olmos-Bustos, Julio García-Cordero, Moisés León-Juárez, Leticia Cedillo-Barron
{"title":"Update on antimicrobial peptides: key elements in <i>Orthoflavivirus</i> infection - an overview.","authors":"Victor Javier Cruz-Holguín, Ivonne Sagrario Romero-Flores, Luis Gerardo Olmos-Bustos, Julio García-Cordero, Moisés León-Juárez, Leticia Cedillo-Barron","doi":"10.1099/jgv.0.002129","DOIUrl":"10.1099/jgv.0.002129","url":null,"abstract":"<p><p><i>Flaviviridae</i> is a family of viruses that are mainly transmitted by mosquito vectors of the genus <i>Aedes</i>, which cause febrile illnesses and, in severe cases, haemorrhagic or neurodegenerative conditions. Over time, these viruses have been reported as emerging pathogens, leading to epidemic outbreaks in various regions worldwide. Additionally, climate change has facilitated the migration of these vectors to regions where they were not previously found. Unfortunately, there are currently no effective treatments or vaccines to prevent or combat <i>Orthoflavivirus</i> infections. Consequently, a deeper understanding of the viral biology and the human host immune response is crucial for advancing the development of therapeutic targets. Amongst the molecules involved in the innate immune response to viral infections are antimicrobial peptides (AMPs), which have been studied for decades. However, their role in <i>Orthoflavivirus</i> infections remains poorly understood. Several researchers have proposed the stimulation or exogenous administration of AMPs during various viral infections, highlighting these molecules as potential innovative therapeutic targets. This study compiles current knowledge on AMPs with a specific focus on <i>Orthoflavivirus</i> infections, emphasizing the importance of these promising therapeutic approaches.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 7","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juan Manuel Castillo, Raymundo Cruz-Pérez, Daniel Talamás-Lara, Juan E Ludert
{"title":"Kinesin light chain 1 interacts with NS1 and is a susceptibility factor for dengue virus infection in mosquito cells.","authors":"Juan Manuel Castillo, Raymundo Cruz-Pérez, Daniel Talamás-Lara, Juan E Ludert","doi":"10.1099/jgv.0.002132","DOIUrl":"10.1099/jgv.0.002132","url":null,"abstract":"<p><p>A hallmark of the dengue virus (DENV) infection is the manipulation of host cell membranes, lipid trafficking and lipid droplets (LD), all cellular functions that depend on the cytoskeleton and the cytoplasmic streaming system. We previously reported the interaction between the DENV non-structural (NS1) protein and members of the kinesin motor complex in the <i>Aedes albopictus</i> cell line C6/36. In this work, we present evidence indicating that the protein kinesin light chain 1 (KLC1) is indeed a susceptibility factor for the DENV replicative cycle in mosquito cells. The interaction between NS1 and KLC1 was confirmed by proximity ligation and co-immunoprecipitation assays in cells harvested 24 hpi. In addition, transmission immunoelectron microscopy showed KLC1 decorating the surface of vacuoles in association with NS1. Increased levels of KLC1 were observed starting at 6 hpi, suggesting that virus infection stimulates KLC1 synthesis. Silencing KLC1 expression results in a reduction in viral genome synthesis, decreased secretion of NS1 and a reduction of virus progeny by nearly 1 log. In agreement, similar affectations were observed in infected cells transfected with a peptide that competes and interferes with the interaction between KLC1 and its cargo molecules. Of note, both silencing the expression and interfering with the function of KLC1 resulted in a disorganization of LD, which decreased in number and increased in area, in mock or infected cells. These results, taken together, suggest that KLC1 is a host susceptibility factor for DENV in mosquito cells and appears to play an important role in the proper transport and homeostasis of LD required for flavivirus replication. However, modest colocalization was observed between NS1 and LD, and the significance of the KLC1 and NS1 interactions needs to be further investigated.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 7","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}