Current Issue
In late 2024, northern China experienced an unexpected surge in human metapneumovirus (hMPV) cases, raising questions about potential novel variants. Kang et al. conducted genomic and evolutionary analyses of hMPV from 2014 to 2024, using data from the Beijing Respiratory Pathogen Surveillance System (RPSS) across 35 sentinel hospitals. They identified lineage I of clade B2 as the main cause of the hMPV outbreak in Beijing from November to December 2024, with no novel variants detected. This study emphasizes the importance of continuous genomic surveillance of respiratory viruses and strengthens preparedness for emerging and re-emerging infectious diseases. The cover image uses a deep-rooted tree to represent the surveillance system, which encompasses epidemiological surveys, medical records, and laboratory test results, with colored leaves and branches illustrating genotype shifts (Kindly designed and provided by Prof. Quanyi Wang and Dr. Lu Kang). See page 48-57 for details.
Current status of dengue fever epidemics and vaccine development
2026, 41(1): 1 doi: 10.1016/j.virs.2026.01.001
Received: 29 May 2025
Accepted: 16 January 2026
Dengue fever, an acute mosquito-borne infectious disease caused by dengue virus (DENV), is primarily endemic in tropical and subtropical regions. In recent years, the global incidence of dengue has increased dramatically. Since 2023, widespread outbreaks have been reported across numerous countries in the Americas, Asia and Africa. According to the World Health Organization, more than 5 million dengue cases were reported globally in 2023, while the number surged to over 14 million cases with more than 10,000 deaths in 2024—marking the highest global burden ever recorded. A similar upward trend has been observed in China, which experienced its largest dengue outbreak in a decade in 2024, with Guangdong Province accounting for the majority of domestically reported cases. These epidemiological patterns highlight the rapid expansion of dengue transmission, driven by climate change, accelerated urbanization and increased human mobility. In this context, vaccine development has become a public health priority. To date, two vaccines—Dengvaxia and Qdenga—have been licensed for clinical use. Six other vaccine candidates are currently in clinical trials, among which the tetravalent live-attenuated vaccines TV003/TV005 are considered the most promising. Despite considerable advances in dengue vaccine research, significant challenges remain, including the need to elicit balanced immune responses against the four serotypes and to reduce the risk of antibody-dependent enhancement (ADE). Taken together, this review systematically summarizes recent global and regional trends in dengue fever and the current progress in dengue vaccine development, collectively offering a valuable resource for informing prevention and control strategies.
The role of T cells in influenza infection and vaccination
2026, 41(1): 10 doi: 10.1016/j.virs.2026.02.005
Received: 05 August 2025
Accepted: 02 February 2026
Influenza virus infections cause significant illness or death every year, becoming a serious health risk. Currently, influenza vaccines mainly induce responses to antibodies against specific strains, but they do not effectively induce effective T cell-mediated immunity. Humoral immunity relies on the production of antibodies that bind to surface proteins (such as hemagglutinin and neuraminidase) to combat the virus. These antibodies envelope the virus to prevent it from invading cells and also label the virus for phagocytic cells to clear. T cell-mediated immunity relies on cytotoxic cells to kill infected cells to combat the virus. Cytotoxic T cells rely on viral proteins on the surface of infected cell to recognize them. This enables the detection of more viral proteins, such as internal proteins like nucleoproteins. A better understanding of the mechanism by which T cells combat influenza is helpful for vaccine development. In this review, we elaborate on the role of T cells in enhancing anti-influenza immune defense. In addition, we explore the possibility that new influenza vaccines can induce such T cell responses.
Advances in human respiratory organoid models for studying the pathogenesis and intervention strategies of COVID-19
2026, 41(1): 23 doi: 10.1016/j.virs.2026.02.002
Received: 19 September 2025
Accepted: 30 January 2026
Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affects multiple organ systems, with the respiratory system being the primary target. Respiratory organoids, which closely mimic the structure and function of the human respiratory tract, have emerged as essential tools for studying SARS-CoV-2 infection. This review summarizes current methods for generating various respiratory organoids, including nasal, tonsil, airway, bronchial, and alveolar organoids, and highlights their application in investigating the mechanism of SARS-CoV-2 infection and evaluating potential therapeutic agents. Meanwhile, this review also introduces respiratory organoid-on-a-chip technology, which can precisely regulate culture conditions and incorporate vascularization and immune cells to enhance physiological complexity, thereby providing crucial support for investigating SARS-CoV-2-induced lung injury, immune responses, and conducting high-throughput drug screening. The aim of this review is to provide valuable insights for further research into the pathogenesis and intervention strategies of COVID-19.
Metatranscriptomics profiling reveals rodent- and shrew-borne viral diversity and evolutionary relationships in Guangzhou, China
2026, 41(1): 35 doi: 10.1016/j.virs.2025.12.009
Received: 05 August 2025
Accepted: 11 December 2025
Emerging zoonotic infectious diseases, predominantly caused by viruses, pose increasing public health threats globally. Rodents and shrews are natural hosts for a variety of zoonotic viruses. Guangzhou is one of China’s most densely populated cities and experiences frequent international and domestic population movements, making it a hotspot for infectious diseases. This study reports the metatranscriptomics virome of 208 rodents and shrews collected between June 2023 and December 2024 from four main urban areas (Tianhe, Baiyun, Liwan, Yuexiu) and five non-main urban areas (Zengcheng, Huadu, Conghua, Panyu, Nansha) in Guangzhou. Individual libraries were constructed from mixed tissue samples (liver, spleen, lung, and kidney) of each animal. Metatranscriptomics sequencing revealed diverse viral communities, identifying 24 viral strains across eight mammalian-associated viral families. Notably, we identified 17 known viruses and seven potentially novel viruses, including Seoul virus (5.2% prevalence in Rattus norvegicus from Panyu), Wenzhou mammarenavirus (13.2% in Rattus norvegicus from Conghua and Huadu), Jeilongvirus (29.4% in Rattus andamanensis from Panyu), and a divergent lineage of arteriviruses that may represent a new genus (maximum positivity rates of 2.9% in Rattus norvegicus and 5.7% in Rattus tanezumi). Phylogenetic analysis elucidated evolutionary relationships within key families such as Hantaviridae, Arenaviridae, Flaviviridae, and Parvoviridae, revealing distinct viral carriage patterns in Guangzhou City that are shaped by host species and geographical location. This is the first macro-level study of rodent and shrew viromes in Guangzhou and provides a scientific basis for strengthening surveillance of mammalian-associated viruses and preventing emerging zoonotic infectious diseases in the region.
Genomic evidence of HMPV resurgence in Beijing: Clade B2 triggers the 2024 winter epidemic peak
2026, 41(1): 48 doi: 10.1016/j.virs.2026.01.006
Received: 20 September 2025
Accepted: 28 January 2026
With an unexpected increase of human metapneumovirus (hMPV) cases in northern China since late 2024, concerns arose whether novel hMPV variants triggered this epidemic. Utilizing the Beijing Respiratory Pathogen Surveillance System (RPSS), we conducted a genomic evolutionary analysis spanning 2014-2024 and revealed genetic information for the strains that caused the high rates of hMPV outbreaks during this period. To clarify the epidemic drivers and evolutionary characteristics of the hMPV strains circulating in Beijing, phylogenetic, population dynamic and mutation analyses were performed using high-quality complete sequences from both this study and publicly available data. A total of 348 high-quality hMPV genomes were obtained by next-generation sequencing (NGS), all of which belonged to four known clades: A2b1, A2b2, B1, and B2. Before 2024, A2b2 predominated in Beijing; however, a shift to clade B2 was observed starting in late 2024. In addition, a phylogenetically independent lineage Ⅰ was identified in this study, accounting for 93.1% of B2 genomes collected since late 2024. Furthermore, we identified several unique nonsynonymous mutations in viruses within lineage I that may have phenotypic implications. Our findings indicate that lineage I of clade B2 was the major cause of the unusual increase in hMPV outbreaks in Beijing in late 2024, with no evidence of an emerging novel variant. Although our data were only restricted to samples from Beijing, the findings are likely representative of the hMPV surge across northern China in 2024, given city's high population density and mobility.
Integrated multiplex PCR and metatranscriptomics reveal upper-lower airway microbial landscapes in pediatric respiratory infections
2026, 41(1): 58 doi: 10.1016/j.virs.2026.02.001
Received: 26 August 2025
Accepted: 28 January 2026
Despite widespread use of multiple PCR, a substantial proportion of pediatric acute respiratory tract infections (ARTIs) lack identifiable pathogens and are classified as unknown etiology. The microbial characteristics and clinical relevance of these cases remain unclear. In this study, we compared the airway microbiomes of PCR-positive and PCR-negative ARTIs and examined their relationships with sampling site and disease severity. A total of 514 hospitalized children with ARTIs were enrolled. Nasopharyngeal swabs (NS) and bronchoalveolar lavage fluid (BALF) samples were tested using a 22-target multiplex PCR panel and subsequently stratified by pathogen status for pooled metatranscriptomic sequencing to profile active microbial communities, viral genotypes, and antibiotic resistance genes. PCR identified common respiratory pathogens in 77.0% of NS and 54.1% of BALF samples. Metatranscriptomic analysis showed that PCR-negative pools displayed markedly lower viral activity and comparatively higher bacterial transcript abundance, with notable enrichment of Pseudomonas. Microbial signatures differed between upper and lower airway samples and across clinical severity, with severe cases demonstrating increased bacterial burden and Pseudomonas enrichment, whereas mild infections exhibited relatively stronger viral signals. Under current thresholds, antibiotic resistance genes were detected in patient pools but not in healthy controls. Overall, PCR-negative pediatric ARTIs exhibited distinct, bacteria-enriched microbial profiles. Integrating metatranscriptomics with PCR enhances pathogen characterization and reveals site- and severity-related microbial patterns that may support diagnostic evaluation and clinical management.
Evidence of human exposure to tick-borne viruses based on viromes of ticks and presence of specific antibodies among patients in Hainan Island, southern China
2026, 41(1): 70 doi: 10.1016/j.virs.2026.02.008
Received: 11 October 2025
Accepted: 09 February 2026
Hainan Island, located in the South China Sea, is known as an area with diseases related to Rickettsia spp. or spirochete infection; however, the potential threat there from infection with tick-borne viruses (TBVs) remains obscure. In the present study, the dominant tick species, including Rhipicephalus sanguineus and Rhipicephalus microplus, were collected in Hainan Island, and tick viromes were investigated by metagenomic sequencing. In total, 27 viral species were identified belonging to the families Orthomyxoviridae, Flaviviridae, Nairoviridae, Phenuiviridae, Totiviridae, Chuviridae, Rhabdoviridae, and Parvoviridae, amongst which one novel virus and 13 new strains were discovered. Subsequently, individual ticks were screened for seven TBVs, Huanggang Rhabd tick virus 1 (HRTV1), Lihan tick virus (LHTV), Mivirus (MIV), Guangdong tick quaranjavirus (GTQV), Wenchang Ephemerovirus (WEPMV), Jingmen tick virus (JMTV), and brown dog tick phlebovirus (BDPTV), resulting in high prevalence rates of 16.97%, 9.59%, 10.33%, 7.38%, 7.01%, 6.27%, and 3.69%, respectively. While co-infection with multiple viruses was more frequent in R. sanguineus, R. microplus ticks generally had higher viral loads. Four febrile patients showed antibody responses to three TBVs, one each to LHTV and JMTV, and two to GTQV; the patient with antibodies to JMTV also showed neutralizing activity against this virus. This study promoted our understanding of the diversity and complexity of the TBV community in Hainan Island. The results provide serological evidence that human exposure to TBVs like JMTV may have occurred in Hainan, raising concern about potential risks from TBVs and the need to perform further surveys of TBVs among ticks, animals and humans.
Characteristics of humoral and T-cell immune responses in people living with HIV after breakthrough SARS-CoV-2 Omicron variant infection during December 2022 to January 2023
2026, 41(1): 84 doi: 10.1016/j.virs.2026.01.003
Received: 31 October 2025
Accepted: 22 January 2026
Due to inherent immune deficiency, the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune responses in people living with HIV (PLWH) following breakthrough infection with remain incompletely elucidated. A large-sample real-world study was conducted from December 2022 to January 2023, which systematically analyzed immune responses in 1367 PLWH and 219 people without HIV (PWOH) by evaluating serum IgG antibody levels against SARS-CoV-2 wild-type strain and Omicron variants, neutralizing antibody titers, as well as the features of SARS-CoV-2-specific T-cell responses in this population. The results demonstrated that the breakthrough Omicron infection rate in PLWH (60.6%) was significantly lower than that in PWOH. Meanwhile, PLWH exhibited notably reduced IgG antibody levels against both the wild-type strain and Omicron BF.7 variant, with a concurrent decline in neutralizing antibody titers. However, fully vaccinated PLWH with CD4+ T-cell counts ≥200 cells/μL achieved post-infection antibody levels comparable to those of PWOH. Notably, PLWH with CD4+ T-cell counts <200 cells/μL or unvaccinated PLWH showed obvious impairment in both humoral and cellular immunity. Although PLWH could maintain relatively high levels of SARS-CoV-2-specific antibodies and T-cell responses within six months after infection, the overall intensity of their immune responses remained lower than that of PWOH. Furthermore, while wild-type SARS-CoV-2 vaccines could effectively elevate antibody levels in PLWH, their protective efficacy against Omicron variants was relatively limited. These findings provide important experimental and clinical evidence for formulating exclusive and targeted SARS-CoV-2 vaccination strategies for PLWH.
Genomic assembly, rescue, and characterization of a functional pseudorabies virus
2026, 41(1): 97 doi: 10.1016/j.virs.2025.11.010
Received: 21 October 2025
Accepted: 26 November 2025
With recent advances in synthetic biology methods, the genomes of several large DNA viruses have been de novo synthesized and assembled, leading to the functional rescue of the respective viruses. Pseudorabies virus (PRV), a large DNA virus belonging to the family Herpesviridae, causes severe diseases in swine, resulting in significant economic losses to the global pig farming industry. Genome editing is crucial for attenuating virulence and developing safer vaccines for PRV. However, its complex repetitive sequences and extremely high GC-rich genome pose significant challenges for genetic manipulation. In this study, we developed a PRV genome assembly platform using yeast-based transformation-associated recombination (TAR) technology. The genome of a prevalent genotype II variant strain, PRV-GX-2011 (GenBank number PV405324.1), was divided into nine A-level fragments and cloned into vectors via TAR. Subsequently, three B-level fragments were generated by recombining three A-level fragments each. In vitro CRISPR/Cas9-mediated editing was introduced to insert an egfp gene into the non-coding intergenic region between UL23 and UL22 genes. Infectious viruses were rescued by co-transfection of linearized B-level fragments in Vero cells, and an isolated virus, PRV-GX-Syn1, was purified via plaque assay. While PRV-GX-Syn1 exhibited reduced viral titer and smaller plaque size compared to the parental strain, its morphological characteristics remained indistinguishable from the parental virus. In BALB/c mice, PRV-GX-Syn1 caused lethal infection, producing lung pathology comparable to the parental strain. This TAR-based platform offers faster and more flexible genomic modification of PRV, facilitating both basic research and PRV-based vaccine vectors.
Development of the reverse genetics system for viral hemorrhagic septicemia virus genotype IVa and its application in antiviral compound screening
2026, 41(1): 107 doi: 10.1016/j.virs.2025.12.010
Received: 05 September 2025
Accepted: 16 December 2025
Viral hemorrhagic septicemia virus (VHSV) is a major pathogen affecting freshwater and marine fish species, posing a significant threat to global aquaculture. Reverse genetics systems are essential for studying viral replication, and host interactions, as well as developing vaccines and therapeutics. In this study, we developed a reverse genetics platform for VHSVLB2018 strain, a genetically distinct VHSV genotype IVa strain which exhibits low genomic identity with other Asian isolates, using a dual RNA polymerase I/II transcription vector. We successfully rescued recombinant VHSV in mammalian (B7GG) and fish (FHM and EPC) cell lines, and engineered recombinant VHSV strains expressing EGFP (rVHSV-EGFP) and cherry (rVHSV-Cherry) fluorescent proteins. Phenotypic analysis revealed that unmodified recombinant VHSV (rVHSV) exhibited growth kinetics and virulence similar to the wild-type VHSV, while fluorescent protein-expressing variants showed attenuated replication and virulence, with the rVHSV-EGFP strain displaying the greatest attenuation. Utilizing the rVHSV-EGFP strain, we conducted antiviral compound screening and identified three promising inhibitors-xanthohumol, octyl gallate, and rottlerin that effectively inhibit VHSV replication. Time-of-addition assays further revealed that xanthohumol and rottlerin targeted the viral replication stage, while octyl gallate interfered with viral internalization. This reverse genetics system provides a versatile platform for studying VHSV pathogenesis, developing live-attenuated vaccines, and screening antiviral compounds, enhancing our understanding of this pathogen and offering new tools for aquaculture disease management.
Enhancing the stability of influenza a reporter viruses by recoding the gfp gene
2026, 41(1): 119 doi: 10.1016/j.virs.2026.01.005
Received: 03 August 2025
Accepted: 27 January 2026
Influenza A virus (IAV) is one of the most important zoonotic pathogens and can cause global influenza pandemics and seasonal influenza outbreaks. Generation of recombinant IAV expressing a fluorescent protein will allow the infection to be easily monitored. In this study, we initially constructed a replication-defective H1N1/△PB2-GFP and a replication-competent H1N1/NS-GFP. However, these two reporter IAVs exhibited genetic instability. To stabilize the recombinant viral genome, we recoded the gfp sequence (rGFP) using synonymous codons to mimic the high-NP-binding regions involved in NP-vRNA interaction. This approach resulted in the development of replication-defective H1N1/△PB2(300)-rGFP and replication-competent H1N1/NS-rGFP, both of which exhibited enhanced stability in GFP expression. By replacing the HA segment from strain A/mink/China/CY 2017 (H5N1), we also generated a replication-defective H5N1/△PB2(300)-rGFP, which showed excellent genetic stability. Using these reporter IAVs, the blocking of virus infection by neutralizing antibodies and antivirals can be rapidly detected by the loss of fluorescent reporter expression. Replication-defective reporter IAVs constructed in this study can only infect and replicate in cells expressing PB2, allowing the possibility of manipulation of highly pathogenic IAV and their related reassortant strains in biosafety level-2 laboratories. Our data highlight the importance of NP-vRNA interaction for the stability of IAV genome, and the reporter IAVs generated using this strategy could be powerful tools for both basic and applied influenza virus research.
Pseudorabies virus TK protein antagonizes alpha interferon response by interfering with the JAK1-STAT1 interaction
2026, 41(1): 132 doi: 10.1016/j.virs.2026.01.004
Received: 02 November 2025
Accepted: 23 January 2026
Pseudorabies virus (PRV), a member of the Alphaherpesvirinae subfamily, is the causative agent of Aujeszky's disease, which severely affects swine health and poses a potential zoonotic risk. PRV can evade the type I interferon (IFN-I)-mediated antiviral response, thus enabling persistent infection, yet the molecular basis for this immune evasion remains unclear. Here, we identify a novel role for thymidine kinase (TK), a key PRV virulence factor, in suppressing IFN-I signaling. Ectopic expression of TK markedly inhibited IFNα-induced transcription and expression of interferon-stimulated genes (ISGs), whereas TK-deficient PRV (PRV-△TK) showed increased sensitivity to IFN-I, elevated ISG expression, and reduced replication following IFNα treatment. Mechanistic analyses revealed that TK interacts with both Janus kinase 1 (JAK1) and signal transducer and activator of transcription 1 (STAT1), disrupting the JAK1-STAT1 complex formation and impairing STAT1 phosphorylation and downstream ISG induction. This inhibition is mediated by amino acids 107-212 of TK, a region independent of its catalytic site, and is essential for its immunosuppressive activity. These findings uncover a previously unrecognized function of TK in antagonizing the IFN-I response through interference with JAK1-STAT1 signaling. Beyond its established role in nucleotide metabolism and virulence, this immune evasion function may account for the strong conservation of TK among PRV strains. Collectively, our results expand the understanding of PRV pathogenesis and identify TK as a potential target for antiviral intervention.
Nuclear translocation of Sp100A suppresses multiple DNA viruses and limits HSV-1 lytic replication in vivo
2026, 41(1): 144 doi: 10.1016/j.virs.2026.02.003
Received: 31 May 2025
Accepted: 30 January 2026
Sp100 (Speckled protein 100 kDa), a key component of promyelocytic leukemia (PML) nuclear bodies, plays a pivotal role in intrinsic and innate immunity. The predominant isoform, Sp100A, has been shown by our previous studies to shuttle between subcellular compartments to enhance innate immunity against RNA viruses and to circulate between cells via extracellular vesicles (EVs) to restrict herpes simplex virus 1 (HSV-1) spread. This study investigates the biological significance of the cyto-nuclear shuttling of Sp100A, a key component of PML nuclear bodies, in antiviral defense against DNA viruses, particularly herpes simplex virus 1 (HSV-1). We demonstrate that Sp100A effectively inhibits multiple DNA viruses in vitro, with its antiviral activity being critically regulated by phosphorylation at the S188 site (a nuclear import-mimicking mutant, S188D, is active, while the S188A mutant is not). Furthermore, DNA virus infection and type I IFN significantly induce Sp100A secretion via extracellular vesicles (EVs), which confers broad, non-IFN-mediated antiviral protection between cells. In a murine model, Sp100A expression significantly reduced HSV-1 lytic replication and clinical signs, but did not impair latency establishment or reactivation potential. These findings underscore the critical role of Sp100A's dynamic shuttling in antiviral defense, showing its activity is specifically restricted to the lytic phase of HSV-1. Sp100A's multifaceted antiviral properties highlight its potential as a novel therapeutic target for combating DNA virus infections.
Single-cell transcriptomic analyses of HSV-1 reactivation from latently infected tree shrew and mouse trigeminal ganglia reveal differing molecular and cellular processes
2026, 41(1): 157 doi: 10.1016/j.virs.2026.02.009
Received: 24 September 2025
Accepted: 09 February 2026
Herpes simplex virus type 1 (HSV-1) infects over 70% of the population and establishes lifelong latent infection with periodic reactivation in humans, resulting in various related diseases. However, the molecular and cellular events underlying the transition of HSV-1 from latency to reactivation remain poorly understood. In this study, we used bulk RNA sequencing and single-cell transcriptomic analyses to dissect the cellular and molecular events of HSV-1 latency-reactivation transition in infected trigeminal ganglia (TG) in both mouse and tree shrew infection models. We found that mice exhibited fluctuating host gene responses during the acute phase and relatively quiescent latency, whereas tree shrews displayed a relatively mild acute phase and active latency characteristics. Single-cell analysis revealed that HSV-1 infects TG neuronal subpopulations expressing growth hormone and pituitary hormones. Importantly, we observed that HSV-1 latency in tree shrew TGs exhibited inhibition of cellular autophagy function, while HSV-1 latency in mice was accompanied by the attenuation of monocyte-related immune surveillance. Given that infected cell protein 0 (ICP0) has autophagy inhibitory activity, we further investigated the role of this viral protein in tree shrew models using an ICP0-deficient HSV-1 strain. Notably, the mutant virus could not undergo spontaneous reactivation from latency. These findings support the hypothesis that ICP0 may be essential for spontaneous reactivation by inhibiting autophagy in vivo.
Desmoglein 2 (DSG2)-knockout human respiratory epithelial cell model to study species B adenovirus receptor usage
2026, 41(1): 172 doi: 10.1016/j.virs.2026.02.007
Received: 25 September 2025
Accepted: 06 January 2026
With an increasing number of human adenoviruses identified, the selection of potential therapeutic vectors broadens. For safety reasons, achieving cell-specific gene delivery is crucial to minimize off-target effects. Therefore, it is essential to gain a systematic understanding of adenovirus receptor-usage. Our aim is to establish a human-originated in vitro model for comparative analysis of human adenoviruses receptor usage. Based on our previous work of human CD46 and coxsackievirus and adenovirus receptor (CAR) knockout cell lines, we generated desmoglein 2 (DSG2) knockout cell lines using genome-engineering technology based on Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9 (CRISPR/Cas9). All together, we established a panel of cell lines that carry a single, double, or triple knockout of the three major human adenovirus receptors: CAR, CD46 and DSG2. Notably, cell proliferation speed was affected by the CAR-knockout, but not the DSG2-or CD46-knockouts. In addition, the spheroid formation ability was sharply reduced in CAR- or DSG2-knockout cells, but not the CD46-knockout cells. With this receptor-knockout model, we confirmed the receptor usage of nine species B adenoviruses. Furthermore, adenovirus vectors containing a previously identified DSG2-binding affinity-enhanced mutation showed DSG2-dependent cell entry within this cell model, which indicates that they are de-targeted from CD46 — the ubiquitously expressed receptor on all nucleated cells. Collectively, our findings show that the adenovirus major receptor knockout cell lines can serve as an in vitro model to help select adenovirus types suitable for individual applications and to better understand adenovirus infection biology.
Multivalent display of envelope protein domain III with Mi3 nanoparticles induces protective immunity against lethal Zika virus infection in mice
2026, 41(1): 182 doi: 10.1016/j.virs.2025.12.012
Received: 23 June 2025
Accepted: 29 December 2025
Zika virus (ZIKV) infection is associated with severe neurological complications such as congenital microcephaly, yet no safe and effective vaccine is currently available. A critical challenge in ZIKV vaccine development arises from cross-reactive, non- or sub-neutralizing antibodies, which may enhance dengue virus (DENV) infection through antibody-dependent enhancement (ADE). Herein, we report a vaccine strategy utilizing Mi3 nanoparticles to display the envelope (E) protein domain III (EDIII) of ZIKV, which induces protective immunity against ZIKV infection in murine models. Compared to an EDIII subunit vaccine, the Mi3-EDIII nanoparticle vaccine elicited significantly higher antibody responses and stronger cell-mediated immune responses. In C57BL/6 mice, maternal immunization with Mi3-EDIII protected the neonates against ZIKV-caused symptoms, including body weight loss, neurological abnormalities, retardation of brain development, and mortality. In interferon-α/β receptor knockout (Ifnar1-/-) C57BL/6 mice, Mi3-EDIII immunization conferred effective protection against lethal ZIKV challenge. Notably, unlike ZIKV convalescent sera, Mi3-EDIII immune sera did not enhance DENV infection in human chronic myelogenous leukemia K562 cells, suggesting the absence of ADE-prone antibody induction. Our results demonstrate that Mi3-EDIII is a promising vaccine candidate against ZIKV infection and warrants further development.
Systematic evaluation of HSV-1 △34.5△47 as a dual-function platform for attenuated HSV-1 vaccine and heterologous antigen delivery
2026, 41(1): 196 doi: 10.1016/j.virs.2026.01.002
Received: 29 June 2025
Accepted: 21 January 2026
Herpes simplex virus type 1 (HSV-1) causes lifelong latent infection and is associated with severe diseases, including herpes simplex encephalitis, neonatal herpes, and no licensed vaccine is currently available for this pathogen. Here, we systematically evaluated an attenuated HSV-1 platform with deletions in ICP34.5 and ICP47 genes (HSV-1 △34.5△47) for application as a dual-function vaccine. This construct, generated by BAC-galK recombination, showed attenuated replication in vitro. Notably, it elicited robust humoral and cellular immune responses in mice, and provided complete protection against lethal challenge with virulent HSV-1 McKrae strain through both corneal and genital tract infection routes. To assess its utility for heterologous antigen delivery, we engineered a recombinant HSV-1 △34.5△47-N, which expresses the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein. This recombinant virus retained the protective efficacy against HSV-1 and induced robust N-specific immune responses. Passive serum transfer and in vivo T-cell depletion studies demonstrated that humoral immunity was sufficient to mediate protective immunity against HSV-1 challenge. Safety assessment revealed no detectable viral mRNA or pathological lesions in the brains of immunized animals. These findings support HSV-1 △34.5△47 as a safe and versatile platform for both HSV-1 prophylaxis and heterologous antigen delivery.
Phloretin targeting the 3CLpro Cys144 exhibits broad-spectrum antiviral activity against swine enteric coronavirus
2026, 41(1): 208 doi: 10.1016/j.virs.2026.02.011
Received: 16 September 2025
Accepted: 12 February 2026
Swine enteric coronaviruses (SECoVs) cause severe watery diarrhea and high mortality in piglets, resulting in significant economic losses to the global pig industry. However, frequent mutations in SECoVs significantly compromise vaccine-induced immunity and limit cross-protection against emerging variants. Therefore, there is an urgent need to develop new broad-spectrum antiviral drugs to be the last line of defense to supplement vaccine immunity. In this study, we utilized molecular docking and molecular dynamics simulations to identify phloretin as a broad-spectrum SECoV inhibitor. Phloretin has demonstrated prophylactic and therapeutic efficacy in vitro and in vivo, improving the survival of SECoV-infected piglets. It was further found that phloretin exerts a broad-spectrum antiviral effect by acting on the conserved 3CLpro Cys144 site of three SECoVs. It is worth noting that derivative A12, designed on the basis of the structure-activity relationship (SAR) between phloretin and 3CLpro, showed a 15.7, 2.6, and 8.4-fold increase in antiviral effect against porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine delta coronavirus (PDCoV), respectively. This study reveals a 3CLpro Cys144 targeting broad-spectrum strategy for use against SECoVs, providing a candidate drug to bridge the vaccine immunity gap.
Emergence and molecular characterization of bovine papular stomatitis virus in Chinese cattle
2026, 41(1): 227 doi: 10.1016/j.virs.2025.12.011
Received: 19 June 2025
Accepted: 26 December 2025
Highlights
1. Virome profiling of calves presenting skin lesions enabled the identification of BPSV, IDV, BRAV, and RVA.
2. The near-complete genome of BPSV/HBSJZ/CHN/2024 showed the highest identity to the Iranian reference strain.
3. Two distinct phylogenetic clades of Chinese BPSV point to at least two independent introductions.
1. Virome profiling of calves presenting skin lesions enabled the identification of BPSV, IDV, BRAV, and RVA.
2. The near-complete genome of BPSV/HBSJZ/CHN/2024 showed the highest identity to the Iranian reference strain.
3. Two distinct phylogenetic clades of Chinese BPSV point to at least two independent introductions.
GP38 is a structural component of Crimean-Congo hemorrhagic fever virus particles
2026, 41(1): 231 doi: 10.1016/j.virs.2026.02.006
Received: 30 September 2025
Accepted: 02 February 2026
Highlights
1. LC-MS/MS analysis indicated comparable levels of GP38 and viral structural proteins (NP, Gn, Gc) in purified CCHFV particles.
2. Western blot and IEM results confirm the presence of GP38 in CCHFV particles.
3. CCHFV particles were imaged and viral morphology was characterized the first time.
1. LC-MS/MS analysis indicated comparable levels of GP38 and viral structural proteins (NP, Gn, Gc) in purified CCHFV particles.
2. Western blot and IEM results confirm the presence of GP38 in CCHFV particles.
3. CCHFV particles were imaged and viral morphology was characterized the first time.
Development of a stable replicon system of a pangolin merbecovirus for antiviral screening
2026, 41(1): 236 doi: 10.1016/j.virs.2026.02.004
Received: 15 October 2025
Accepted: 02 February 2026
Highlights
1. A replicon of the pangolin HKU4-related coronavirus (MjHKU4r-CoV-1) containing a nanoluciferase reporter gene was constructed.
2. A stable BHK21 cell line carrying the replicon has been generated.
3. This replicon system has been effectively employed in testing the antiviral activity of replication-targeting coronavirus drugs.
4. It offers a safe, efficient and convenient tool for screening antivirals against MjHKU4r-CoV-1 and other coronaviruses.
1. A replicon of the pangolin HKU4-related coronavirus (MjHKU4r-CoV-1) containing a nanoluciferase reporter gene was constructed.
2. A stable BHK21 cell line carrying the replicon has been generated.
3. This replicon system has been effectively employed in testing the antiviral activity of replication-targeting coronavirus drugs.
4. It offers a safe, efficient and convenient tool for screening antivirals against MjHKU4r-CoV-1 and other coronaviruses.
GlycoRNAs: Biological functions and novel antiviral targets
2026, 41(1): 240 doi: 10.1016/j.virs.2026.02.010
Received: 23 September 2025
Accepted: 11 February 2026
Highlights
1. GlycoRNAs on host cell surfaces serve as adhesive molecules for viral internalization.
2. GlycoRNAs may interact with immunomodulatory receptors and facilitate immune recognition and responses.
3. Targeting glycoRNAs shows promise for antiviral therapy.
1. GlycoRNAs on host cell surfaces serve as adhesive molecules for viral internalization.
2. GlycoRNAs may interact with immunomodulatory receptors and facilitate immune recognition and responses.
3. Targeting glycoRNAs shows promise for antiviral therapy.
