Journal of General Virology最新文献

{"title":"Evolutionary and molecular characteristics of high-Shannon entropy codons in VP1 of Coxsackievirus A6.","authors":"Han Mo, Hui Li, Liu Yi, Ke Qian, Juan Lin, Ziqi Lin, Fenglan He, Xian Zhang, Xiansheng Ni, Xianfeng Zhou","doi":"10.1099/jgv.0.002306","DOIUrl":"10.1099/jgv.0.002306","url":null,"abstract":"<p><p>Coxsackievirus A6 (CVA6) has emerged as a predominant global pathogen of hand, foot and mouth disease, yet its evolutionary and molecular characteristics remain poorly understood. This study integrated 10 year molecular surveillance data from central China (2013-2024) with global CVA6 sequences to analyse high-entropy codons in the VP1 capsid protein and their co-evolution patterns. Phylogenetic and Bayesian evolutionary analyses indicated that CVA6 strains in China primarily clustered into sub-genotype D3, with an estimated global VP1 substitution rate of 3.62×10⁻³ substitutions/site/year. Shannon entropy analysis identified eight high-Shannon entropy codons in VP1 (sites 5, 29, 30, 97, 137, 174, 242, 283), with site 283 exhibiting the highest variability. A novel 283V variant (<i>n</i>=12) was uniquely detected in China after 2018. Direct-coupling analysis suggested co-evolution between residue pairs, most notably VP1-137 and VP1-242 (Direct information=0.44), where S137N may form new hydrogen bonds with 243 h, potentially contributing to structural changes that could influence immune evasion. Furthermore, S97N formed hydrogen bonds with D99, thereby altering the BC loop region. A spatiotemporal analysis showed that 283A replaced 283T on a global scale after 2017, while minor variants (e.g. 30D, 97I, 174A) exhibited localized circulation. These findings highlight the predominance of high-entropy codons in VP1 surface loops (BC, DE, EF and HI), suggesting ongoing adaptive selection pressure. Continuous genomic surveillance is imperative for tracking emerging variants (e.g. 283V, 97N) and for informing vaccine design against evolving CVA6 strains.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620253","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":"Quantitation of cytopathic honey bee viruses using the viral plaque assay method.","authors":"Alexander McMenamin, Michael Goblirsch","doi":"10.1099/jgv.0.002304","DOIUrl":"10.1099/jgv.0.002304","url":null,"abstract":"<p><p>Viral pathogens are highly prevalent threats to our pollination workforce. Basic virological techniques for ascertaining infection intensity and quantifying infectious viral particles lag behind the research interest in pollinator-associated viruses. Here, we utilized the only available immortalized honey bee (<i>Apis mellifera</i>) cell line, AmE-711, to establish the first plaque assay protocol for a bee-infecting virus in honey bee cells. First, we demonstrate that AmE-711 is susceptible to acute bee paralysis virus (ABPV) despite being persistently infected with deformed wing virus. Then, we compared two traditional overlays, agarose and carboxymethyl cellulose (CMC) and found that the CMC method was superior in producing countable plaques in ABPV-infected monolayers. Lastly, we demonstrated that this method was useful in quantifying infectious particle loads in lysates derived from whole honey bee pupae infected with ABPV, a field-relevant sample type.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604137","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":"GRHAL1, a novel lncRNA, regulates HIV-1 gene expression by modulating Tat- and Sp1-mediated HIV-1 LTR activation.","authors":"Mohammad Ishaq, Heather Marshall, Ven Natarajan","doi":"10.1099/jgv.0.002288","DOIUrl":"10.1099/jgv.0.002288","url":null,"abstract":"<p><p>We recently reported that GADD34, an integrated stress response (ISR)-associated protein expressed at low levels in many cell lines, functions as a novel HIV-1 restriction factor. To elucidate the mechanism underlying GADD34-mediated inhibition of HIV replication, we investigated the role of long non-coding RNAs (lncRNAs). Here, we identify and characterize a novel lncRNA, GRHAL1 (GADD34-regulated HIV accessory lncRNA-1), which is highly expressed in GADD34-knockout (GADD34-KO) cells relative to WT cells. GRHAL1 is expressed at low basal levels in Jurkat and MT-2 CD4⁺ T cell lines and in primary human CD4⁺ T cells and is upregulated following HIV-1 infection. T cell activation signals that promote HIV-1 replication also induced GRHAL1 expression; however, this induction was independent of IFN and ISR signalling. Transfection of <i>in vitro</i> - synthesized GRHAL1 significantly enhanced HIV-1 LTR-driven gene expression from both integrated and unintegrated promoters. GRHAL1 stimulated both Tat-independent and Tat-dependent LTR activation, with a more pronounced effect observed at suboptimal Tat levels, indicating functional synergy between GRHAL1 and Tat under limiting Tat conditions. Mutational analysis of the LTR demonstrated that GRHAL1-mediated activation requires an intact Tat-responsive TAR element and upstream Sp1-binding sites, linking GRHAL1 activity to Tat and Sp1 in transcriptional regulation. This synergy was further confirmed using a minimal HIV-1 promoter containing Sp1 sites and a TAR sequence. Moreover, GRHAL1 alone was sufficient to activate a heterologous promoter containing Sp1-binding elements. The Sp1-selective inhibitor mithramycin suppressed both Tat-independent LTR activation and the cooperative activation mediated by GRHAL1 and Tat. Electrophoretic mobility shift assays, RNA immunoprecipitation and RNA-pulldown experiments demonstrated that GRHAL1 directly interacts with Sp1 and that Tat enhances this interaction, suggesting that GRHAL1 modulates Sp1 activity through direct binding. In summary, we identify GRHAL1 as a novel HIV-1-induced lncRNA that regulates viral gene expression by interacting with Sp1 and synergizing with Tat to enhance HIV-1 transcription.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375861","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":"Endolysosomal two-pore channels regulate a conserved entry pathway for enteroviruses.","authors":"Ta-Chou Weng, Bang-Yan Hsu, Tung-Heng Wu, Xin-Ya Gu, Hsu-Hung Cheng, Szu-Hao Kung","doi":"10.1099/jgv.0.002294","DOIUrl":"10.1099/jgv.0.002294","url":null,"abstract":"<p><p>Enteroviruses are significant human pathogens for which there are currently no effective antiviral therapies available. Two-pore channels (TPCs) are endolysosomal cation channels activated by nicotinic acid adenine dinucleotide phosphate (NAADP). These channels play a crucial role in regulating vesicular calcium (Ca²⁺) signalling and endolysosomal membrane trafficking. While endolysosomal TPCs have been implicated in the infectivity of some enveloped viruses, their role in non-enveloped virus infections remains unclear. In this study, we identify human TPC isoforms TPC1 and TPC2 as essential host factors that enhance enterovirus infection by regulating endolysosomal trafficking. Inhibiting NAADP-evoked Ca²⁺ signalling pharmacologically or using CRISPR/Cas9 to knockout either TPC isoform significantly suppressed the replication of enterovirus 71. Mechanistically, the loss of TPC function did not affect the viral binding, internalization or post-entry RNA translation and replication; instead, it delayed the viral progression through early and late endosomal compartments. Live-cell Ca²⁺ imaging confirmed that TPC-dependent NAADP signalling is necessary for endolysosomal Ca²⁺ release during infection. Our data also suggest cepharanthine, a bisbenzylisoquinoline alkaloid, inhibits enterovirus infection partly by modulating TPC-mediated Ca²⁺ signalling. Notably, the pharmacological inhibition or depletion of TPCs broadly restricted the replication of various enterovirus serotypes. Transcriptomic profiling revealed that the disruption of TPC1 or TPC2 alters gene networks associated with endocytosis and vesicular trafficking, emphasizing the vital role of TPCs in maintaining endolysosomal homeostasis. In summary, these findings establish TPC-dependent Ca²⁺ signalling as a conserved host pathway that enteroviruses exploit and highlight endolysosomal TPCs as promising targets for the development of broad-spectrum antiviral strategies.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447521","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":"Tymoviruses partition selection using overlapping genes to allow their replication genes and their movement protein gene to evolve independently.","authors":"A J Gibbs, M J Gibbs, H M Gibbs, M Hajizadeh","doi":"10.1099/jgv.0.002297","DOIUrl":"https://doi.org/10.1099/jgv.0.002297","url":null,"abstract":"<p><p>Viral populations evolve as 'negative selection' removes mutants with harmful changes and 'positive selection' preserves mutants with advantageous changes. How do viruses with small genomes, like tymoviruses, resist mutational changes to their most essential functions, such as replication, but remain evolutionarily flexible enough to acquire new hosts and respond to changes in their environment? Tymoviruses have cytosine-rich genomes and a composition that is notably constant throughout their length, suggesting that their unusual composition is driven by a single process. In contrast, the composition of their proteome, which is rich in leucine, proline and serine, varies more, as one would expect, as its individual proteins are selected for different functions. The main genomic ORF encodes the replication proteins and has been shown to be strongly conserved under negative selection, whereas nearly all positively selected sites occur in the movement protein (MP), which is encoded by a gene that overlaps the 5'-terminal third of the main ORF and is in its +1 reading frame. We found that the MP is an intrinsically disordered protein (IDP) especially rich in proline and serine. Patristic distance comparisons of the ORFs of different tymoviruses showed that their replication proteins differ least, the MPs an intermediate amount and the other IDPs most. The MP exploits the bias towards proline and serine to maintain an intrinsically unstructured state, which is presumably required for its functions, whereas the replication proteins have fewer disorder-promoting amino acids and hence preserve the structure required for their enzymatic functions. Thus, tymoviruses conserve the replication proteins in their main reading frame but use frame-shifting and genetic code redundancy to allow positive selection and evolutionary flexibility of the MP.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562189","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}

{"title":"A P-type pentatricopeptide repeat-containing protein interacts with the Japanese soil-borne wheat mosaic virus movement protein and modulates susceptibility to infection.","authors":"Claudia J Strauch, Khalid Amari, Steffen Ostendorp, Ruth Veevers, Emmanuel Boutant, Nico Sprotte, Richard J Morris, Julia Kehr, Annette Niehl","doi":"10.1099/jgv.0.002260","DOIUrl":"10.1099/jgv.0.002260","url":null,"abstract":"<p><p>As obligate intracellular pathogens, plant viruses interact with host factors to achieve efficient replication and spread. Host factors also play important roles in virus detection and antiviral defence. Furoviruses cause substantial losses in cereals and efficient control measures are lacking. We therefore used Japanese soil-borne wheat mosaic furovirus movement protein (MP^JSBWMV) in immunoprecipitation experiments to identify host interaction partners in the model host plant <i>Nicotiana benthamiana</i>. We identified a P-type pentatricopeptide repeat-containing protein (NbPPR) as the interaction partner of the MP^JSBWMV. Fluorescent protein-tagged NbPPR localized to chloroplasts and to the cytosol and plasmodesmata (PD) depending on the location of the fluorescent protein tag, suggesting that the protein may be dually localized to these cellular compartments. MP^JSBWMV:RFP and GFP:NbPPR colocalized and interacted at PD as shown by fluorescence resonance energy transfer fluorescence lifetime imaging and co-immunoprecipitation. To functionally characterize the MP^JSBWMV-interacting NbPPR, we immunoprecipitated GFP:NbPPR-interacting RNAs and identified a motif overrepresented in the GFP:NbPPR-bound RNAs. The motif is consistent with the PPR target sequence predicted using PPR code. While most of the RNA targets encode subunits of the organellar NADH-dehydrogenase complex, we also identified RNAs encoding cell wall proteins. Downregulation of NbPPR, using virus-induced gene silencing and subsequent infection with fluorescent protein-tagged viruses, resulted in increased numbers of infection sites for JSBWMV in plants silenced for NbPPR compared to controls. We propose a model to explain how virus infection may affect NbPPR function and how NbPPR may regulate the infection cycle. As PPRs are increasingly explored for the modulation of gene expression, virus-targeting PPRs may be developed into tools for virus control in future.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156849","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":"Structural basis of porcine reproductive and respiratory syndrome virus 2 neutralization by a GP4-targeting monoclonal antibody.","authors":"Barbora Veselkova, Chandamita Saikia, Sebastian Affeldt, Sandra Barth, Manoj Kumar Rajak, Frithjof Besa, Daria Bezbakh, Guido Hansen, Till Rümenapf, Matthias Ballmaier, Oliver Dittrich-Breiholz, Holly Bamber, Kumar Nagarathinam, Alexander W Tarr, Benjamin Lamp, Thomas Krey","doi":"10.1099/jgv.0.002284","DOIUrl":"10.1099/jgv.0.002284","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) is a genetically diverse RNA virus that causes reproductive failure and respiratory disease in pigs, leading to major economic losses worldwide. Although inactivated and live-attenuated vaccines are available, they provide only partial protection, allowing endemic circulation, persistent transmission and recurrent outbreaks. The limited efficacy of current vaccines reflects the incomplete understanding of immune correlates of protection. Here, we describe a murine monoclonal antibody (IgG #18) with potent, strain-specific neutralizing activity against PRRSV-2. Epitope mapping localized its binding site to the N-terminal region of the minor glycoprotein GP4. Functional and biochemical analyses demonstrated high-affinity binding and effective neutralization, while crystallographic studies revealed its atomic structure in complex with an epitope peptide. To our knowledge, this structure provides the first structural snapshot of a neutralization epitope within the PRRSV glycoproteins, providing insights into the conformation of this key component of the PRRSV envelope complex. This structure also explains the restricted specificity of IgG #18, highlighting the challenge of epitope variability across PRRSV species. Our findings advance understanding of antibody-mediated neutralization and provide an initial framework for the use of structural information in the design of next-generation immunogens aimed at eliciting protective responses against genetically diverse PRRSV strains.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317646","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":"Conserved histidine residues and the control of tick-borne encephalitis virus maturation.","authors":"Iris Medits-Weiss, Lena Roßbacher, David N Springer, Franz X Heinz, Karin Stiasny","doi":"10.1099/jgv.0.002286","DOIUrl":"10.1099/jgv.0.002286","url":null,"abstract":"<p><p>The maturation and infectivity of orthoflaviviruses is driven by interactions and structural changes of the two envelope proteins, prM and E, which are controlled by protonation and deprotonation events during the viral life cycle when the virus encounters acidic and neutral pH environments inside and outside the cell. Histidine residues act as sensors for these pH-induced conformational transitions, which differ between mosquito-borne and tick-borne orthoflaviviruses in some aspects. We identified six histidine residues that are conserved among the envelope proteins of mammalian tick-borne orthoflaviviruses, but not among those of mosquito-borne orthoflaviviruses. These residues might account for some of the structural differences observed between these two orthoflavivirus groups. We therefore conducted a mutational analysis by replacing each of the conserved histidine residues with alanine and determined the effect of these mutations on the maturation and infectivity of tick-borne encephalitis virus (TBEV). One of the histidine residues (H208, located in an insert unique to mammalian tick-borne orthoflaviviruses at the prM-binding site in E) was shown to be an important determinant of efficient prM cleavage. In line with recent findings regarding the infectivity of immature tick-borne orthoflaviviruses, this mutant was only slightly less infectious than the mature wild-type virus. The presence of histidine residue 208 appears to be linked to the particular requirements of the complex ecological life cycle of TBEV and likely reflects an evolutionary adaptation to the specific interactions of the virus with mammalian hosts and/or tick vectors.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13278375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271809","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":"A novel antiviral strategy targeting human metapneumovirus through pH modulation in human airway epithelial cells.","authors":"Ivana Alisandrea Daniels, Benjamin Gaston, Jessica Saunders, Laura Smith, Taiya Whitlow, Nastaha L Tilston, Ryan F Relich, Andrew Lunel, Michael D Davis","doi":"10.1099/jgv.0.002274","DOIUrl":"10.1099/jgv.0.002274","url":null,"abstract":"<p><p>Human metapneumovirus (hMPV) is a major cause of respiratory infections, particularly in vulnerable populations, yet no approved vaccines or targeted antivirals are available. pH-regulated processes, including airway epithelial physiology, endosomal acidification and viral fusion mediated by the fusion (F) protein, are critical for hMPV infection. This study evaluates PHOH-001, an inhaled alkaline buffer, as a potential therapeutic strategy to modulate airway pH and inhibit hMPV infection. Using rhMPV-GFP (green fluorescent protein-expressing hMPV), viral replication was assessed in primary human airway epithelial cells (HAECs). PHOH-001 significantly reduced GFP expression at 72 h post-infection in both submerged and air-liquid interface cultures, with effects comparable to those of the endosomal acidification inhibitor bafilomycin A1. In Vero E6 cells, PHOH-001 increased extracellular and intracellular pH in a dose-dependent manner and correspondingly reduced hMPV infection. In HAECs, PHOH-001 treatment reduced early virus-cell interactions, as measured by decreased cell-associated viral RNA under conditions restricting internalization. PHOH-001 also reduced viral replication, as measured by TCID₅₀ assays and decreased syncytium formation. In parallel, PHOH-001 increased endosomal pH, consistent with altered endosomal acidification. Furthermore, PHOH-001 altered F protein localization and coincided with changes in actin organization, consistent with impaired viral spread. Collectively, these findings indicate that PHOH-001 modulates multiple pH-dependent steps in hMPV infection <i>in vitro</i> and support airway pH modulation as a potential antiviral strategy against hMPV.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13232866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156862","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":"Sensing the storm: how inflammatory signalling drives reactivation of the human cytomegalovirus major immediate-early promoter.","authors":"Benjamin A Krishna","doi":"10.1099/jgv.0.002276","DOIUrl":"10.1099/jgv.0.002276","url":null,"abstract":"<p><p>Seventy years after the discovery of human cytomegalovirus (HCMV), perhaps its most influential contribution to molecular biology remains the major immediate-early promoter (MIEP). A modified form of this powerful regulatory element is now used ubiquitously in biotechnology to drive protein expression, yet within the virus itself, the full promoter performs a far more complex task: governing the balance between latency and lytic replication. This review discusses our understanding of the transcription factors that regulate MIEP activation and repression and how this regulatory network shapes HCMV latency and reactivation.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13322095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352185","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}