The World Health Organization has updated the Priority Pathogens List based on risk assessments of the world’s endemic pathogens, the majority of which are viruses. This assessment proposed to extend research and preparation to the entire families of Priority Pathogens, rather than just focusing on individual known high-risk pathogens. The 21 viruses on the Priority Pathogens List belong to 13 virus families. Viruses within the same family have similarities in genes, immunogens, immunity, and transmission, etc. A protective immunogen is an antigenic component that can induce a protective immune response in the immune system after the invasion of pathogenic microorganisms, and it always serves as the early focal point of vaccines and treatment method developments during an outbreak. Here, we summarized the protective immunogens of Priority Pathogens, found the common features of protective immunogens of viruses in the same family, and proposed that the development of vaccines and screening of neutralizing antibodies based on this clue may be applied to the prevention and control of the epidemics or even pandemics of these Priority Pathogens.
Although COVID-19 pandemic has no longer been classified as an international public health emergency of concern after May 2023, multiple variants with different characteristics keep emerging, especially considering the recently low-level circulation of BA.3.2. Given the complex spatial–temporal characteristics of epidemics, responding to potential changes in variants is a significant public health challenge. Serotypes are defined as unique variants within specific immune response characteristics, which are used in the study of various pathogens. The sero-epidemiological features of COVID-19 may offer a new perspective for variant surveillance and public health preparedness. Based on the global SARS-CoV-2 genome deposition data in Our World in Data (OWID) based on GISAID from March 1, 2021 to May 3, 2024, we analyzed the epidemic features of different variants based on the serotype concept and combined with cross-sectional studies. In the dataset comprising variants from 58 countries or regions with complete information, we calculated the median duration times of epidemic, the median epidemic peak times for Serotypes Ⅱ-Ⅴ and the median alternation times of epidemic for Serotypes I-Ⅱ to Ⅴ-Ⅵ respectively. An increasing trend was observed during these time period between the epidemics of Serotypes Ⅱ, Ⅲ, Ⅳ and Ⅴ, except the longer duration time for Serotype I. By constructing a regression and curve regression equation, the potential emerging of a new serotype can be explored, and a possible time window for its emergence— around 2025, or even later, which may match with the emerging of BA.3.2. The gradually-increased prevalence periods for SARS-CoV-2 serotypes except Serotype I may suggest a slowing down mutation rate. Understanding the epidemic time of different serotypes can provide insight into the surveillance and forecasting of COVID-19.
Since its emergence in late 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has continuously threatened human health through constantly arising variants with iterative immune escape abilities. While SARS-CoV-2 variants have been recently classified into six serotypes based on cross-reactive antibody responses, T cell response features against these serotypes remain largely unknown. We evaluated SARS-CoV-2 spike-specific T cell responses among convalescents infected by three different strains (prototype, BA.5.2/BF.7, and XBB/EG.5.1) against SARS-CoV-2 prototype and 15 subvariants covering all six serotypes. Generally, cross-reactive T cells could recognize variants within the same serotype, but they also mounted weaker responses to variants from subsequent serotypes. Serotype I (prototype) convalescents showed lower T cell responses against Omicron variants (Serotype II to IV), with cross-reactive T cell gaps between different serotype strains, i.e. Serotype II > III > IV. Serotype IV (BA.5.2/BF.7) convalescents exhibited weaker T cell responses to Serotype V (XBB/XBB.1.5/XBB.1.16/EG.5.1) strains and even lower responses to Serotype VI (BA.2.86/JN.1) strains. Similarly, Serotype V (XBB) convalescents showed significantly weaker cross-T cell responses to the Serotype VI (BA.2.86) strains than to the Serotype V strains. We also identified key serotype-signature mutations in T cell epitope hotspot regions that could attenuate CD8+ and/or CD4+ T cell recognition, potentially underlying SARS-CoV-2 serotype-associated T cell immune evasion mechanisms. Our findings reveal the pivotal role of population T cell immune barrier against emerging SARS-CoV-2 variants in a serotype-associated pattern and provide insights into the T cell-oriented universal vaccine development for coronaviruses.
Maximum biosafety level laboratories, also known as Biosafety Level 4 (BSL-4) laboratories are pivotal to advancing basic research and technological innovation for preventing and treating infections caused by maximum biosafety level pathogens. Herein, we conduct a bibliometric analysis to identify global research trends and hotspots in this field, with the aim of guiding future scientific strategy and fostering international collaboration. A total of 604 relevant English publications (1980–2025) from the Web of Science Core Collection were analyzed using CiteSpace, VOSviewer, and the bibliometrix R package. The results delineate a two-phase growth pattern: annual publication output transitioned from a prolonged period of slow growth to a sustained high-output plateau following the 2014–2016 Ebola epidemic. Ebola virus is the most frequently studied pathogen, while the Journal of Infectious Diseases is the most prolific journal. Keyword analysis revealed an evolution in research focus from basic research towards applied medical countermeasures, with current priorities centered on evaluating the safety and efficacy of vaccines. The United States emerged as the dominant force, producing the leading institutions, core researchers, and maintained a robust collaborative network with partners like Canada and Germany that significantly outpaced Asian countries. This concentration of research effort, observed within our pathogen cohort, underscores the need for more balanced global cooperation focused on a wider spectrum of maximum biosafety level pathogens.
Background:Continuous SARS-CoV-2 Omicron emergence poses challenges to immune protection from the previous infection/vaccination in the population. While neutralizing antibodies serve as a key immune protection indicator, their cross-protective effect against novel variants remains limited. However, T cell immunity may confer more durable and broad-spectrum protection. Methods:We evaluated immune dynamics in four Chinese cohorts comprising BF.7/BA.5.2, XBB, and JN.1 convalescents, plus tetravalent recombinant protein vaccine recipients. Neutralizing antibodies were assessed against nine variants spanning the emerging evolutionary spectrum. T cell responses were characterized using variant-specific peptide pools. Antigenic relationships were analyzed through multidimensional scaling-based cartography. Results:BF.7/BA.5.2 convalescents exhibited progressive antibody evasion, with fold-changes against heterologous variants increasing from 4-12-fold initially to > 20-fold at 6 months. XBB convalescents maintained stable short-term responses, while JN.1 convalescents showed superior cross-reactivity against descendant lineages. BA.3.2 demonstrated maximal immune evasion across all groups, occupying the most distant antigenic position. In contrast, T cell immunity exhibited remarkable stability and cross-reactivity, maintaining elevated levels at 6 months with balanced responses against all tested variants. The tetravalent vaccine induced broad-spectrum T cell responses comparable to natural infection, and elicited cross-neutralizing antibody responses against different Omicron variants. Discussion:Our study reveals SARS-CoV-2 variant-specific antibody escape compensated by stable cross-reactive T cell responses. In the context of continued viral evolution, stimulating robust T cell immune responses may be critical to achieve a high population immune barrier against future coronaviruses/variants. These findings emphasize the necessity of comprehensive immune evaluation integrating both humoral and cellular components and provide scientific foundations for optimizing vaccine strategies and immune surveillance systems to address emerging viruses and their variants.
Nipah virus (NiV) and Langya virus (LayV) are emerging zoonotic henipaviruses with serious public health risks. However, no vaccine or drug is available for either disease. To address the persistent threats posed by NiV and LayV, we preliminarily developed indirect ELISAs based on truncated fusion glycoprotein (F) and attachment glycoprotein (G) expressed in a mammalian expression system. We validated these assays using immunized BALB/c mice (for both NiV and LayV), immunized Syrian golden hamsters (for NiV), and goats and a dog that were naturally infected (for LayV). Specificity was assessed using negative sera from mice, ferrets, African green monkeys, hamsters and swine. The ELISAs demonstrated high sensitivity (1:64,000) for both viruses in immunized BALB/c mice, high specificity (approximately 95% in mice and 100% in ferrets, African green monkeys, hamsters and swine), and strong concordance with commercial NiV ELISA kits (>93%). The NiV ELISAs were further validated using immunized Syrian golden hamsters, which had sensitivities of 1:51,200 (F-based) and 1:6400 (G-based). The LayV ELISAs successfully detected antibodies in the sera of goats and a dog naturally infected with LayV. These preliminary indirect ELISAs serve as proof-of-concept tools and may be valuable for vaccine and therapeutic development, serological surveillance studies and future diagnostic platform development.
As one of the earliest identified susceptible animals for the SARS-CoV-2, cats are also the vulnerable hosts for feline coronaviruses, ie feline enteric coronavirus (FECV). Here, to understand the cross-presentation of coronavirus-derived peptides by cat major histocompatibility complex molecule feline leucocyte antigen (FLA) class I, unpredictable natural peptide motifs presented by FLA-K*00701 and FLA-E*00301 were identified through peptide elution and further confirmed by the structural determination of the 2 FLA class I molecules. Based on these precise motifs of FLA class I peptides, the atlas of cross-presenting peptides from different coronaviruses in cats were sketched with 3 hotspots in C-terminal half of ORF1ab protein. The possibility of cross-presentation is further supported by the similar conformation of the corresponding peptides KP-CoV-9 (RSFIEDLLF) and KM-FECV-9 (RSAVEDLLF) from the 2 coronaviruses presented by FLA-K*00701. Our findings provide insights into the understanding of the cross-presentation of peptides from SARS-CoV-2 and feline coronaviruses FECV and the development of universal vaccine for coronaviruses.
Acute viral infections may lead to long-term adverse health effects. Investigating the hematological and biochemical profiles during recovery can provide valuable insights into the prognosis of severe fever with thrombocytopenia syndrome (SFTS) virus infection. Herein, we performed a cross-sectional analysis of 24 hematological parameters and 12 liver and kidney function-related indicators in 143 naturally infected SFTS patients from the acute phase to 10 years post-recovery. Statistical analyses were performed using the Chi-square test ( χ 2), Fisher’s exact test, or the ANOVA with Bonferroni correction to assess group differences. Most indicators gradually recovered over time during the recovery period. The decrease in platelet (PLT), white blood cell, neutrophil (NEU), and lymphocyte counts in the acute phase showed a gradual recovery trend from 1-8 months to 6-10 years post-recovery. PLT count levels positively correlated significantly with recovery duration ( P = 0.0149). NEU % and thrombocytocrit continued to improve with the recovery time. In addition, some indicators, including platelet distribution width, mean platelet volume, and mean corpuscular hemoglobin concentration, continued to show abnormalities in a certain proportion (12.9 %-69.8 %) of individuals post-recovery. For liver and kidney function-related indicators, acute-phase elevations in aspartate aminotransferase and alanine aminotransferase resolved progressively. Direct bilirubin showed a gradual upward trend over time. Additionally, persistent reductions in total protein and albumin were observed in a subset of recovered individuals. These findings highlight the need for long-term monitoring of SFTS survivors and inform clinical management strategies.
ObjectiveThis study aims to address the research gaps in understanding the connections between climate change and infectious diseases by integrating bibliometric analysis with epidemiological perspectives and systematically identifying research trends and thematic evolution in this field.MethodsWe conducted a comprehensive bibliometric analysis of literature published between January 2010 and April 2025, retrieved from Web of Science, PubMed, CNKI, and Wanfang databases. Analytical methods included keyword co-occurrence mapping and cluster analysis using CiteSpace and VOSviewer.ResultsThe analysis revealed a steady increase in publication output, accompanied by a notable shift from single-disease studies to complex system assessments. Research patterns showed distinct thematic priorities: vector-borne diseases demonstrated significant growth after 2018; respiratory infections maintained consistent research attention, while enteric diseases received comparatively limited focus. These patterns reflect underlying socioeconomic disparities and regional climatic influences.ConclusionThis study underscores the need for more systematic research on the intersection of climate change and infectious diseases. Future work should develop multi-disease analytical frameworks, advance interdisciplinary methods integrating environmental and data sciences with public health, and strengthen global research networks by improving geographic coverage and data standardization. These efforts will enhance predictive capabilities and intervention strategies against climate-sensitive infectious diseases.
Type I interferon (IFN) signaling is a central antiviral defense, with STAT2 driving the expression of IFN-stimulated genes (ISGs) to restrict viral infection. Many flaviviruses, including Zika virus (ZIKV), evade this pathway through non-structural protein 5 (NS5)-mediated ubiquitination and proteasomal degradation of STAT2, yet the contribution of this immune evasion strategy to viral fitness and pathogenesis remains incompletely defined. Here, using a multi-step mutational scanning strategy that jointly assessed STAT2 degradation and viral RNA replication, we identified a single NS5 residue, L162, as uniquely permissive to substitution that abolishes STAT2 degradation without compromising intrinsic replication functions. Substitution of L162 with alanine or glycine (L162A or L162G) selectively disrupted NS5 recruitment of the ZSWIM8-CUL3 E3 ubiquitin ligase, thereby preserving STAT2 stability and restoring IFN signaling. Recombinant ZIKV carrying these mutations exhibited reduced replication and enhanced ISG induction in human cells, defects fully rescued by STAT2 knockout. In A129 mice (type I IFN receptor deficient), mutant and WT viruses replicated comparably, but in human STAT2 knock-in mice, ZIKV-NS5 L162G exhibited markedly reduced viral loads and disease. Notably, infection with ZIKV-NS5 L162G elicited robust neutralizing antibody and T cell responses that conferred protection against WT challenge. Together, these findings establish NS5-mediated STAT2 degradation as a central determinant of ZIKV immune evasion, viral fitness and pathogenesis, and highlight disruption of NS5-STAT2 antagonism as a promising strategy for antiviral intervention and rational attenuation.
Respiratory syncytial virus (RSV), a major cause of acute respiratory infections (ARIs) globally, poses a significant threat, especially to vulnerable populations. However, the spatial transmission dynamics of RSV strains, including the influence of environmental and socioeconomic factors, remain inadequately understood. This study applied genetic sequences and phylogenetic methods to quantify evolutionary and spatial dispersal dynamics of RSV subgroup A (RSVA) across China from 2011 to 2019. We assessed viral population trends, mapped interprovincial transmission patterns, and evaluated the influence of meteorological and socioeconomic factors on viral spread. Our results revealed cyclical fluctuations in effective population size every 3-5 years, and a predominant southward spread driven by interprovincial transmission networks. We found that higher winter relative humidity (RH), urbanization rate, and human mobility promoted viral spread, while higher winter temperature and elevated urban population density appeared to inhibit it. These findings provide crucial insights into RSVA dispersal in China, underscoring the importance of regional surveillance networks and targeted interventions to curb cross-regional spread, and offer a valuable framework to inform RSV vaccine rollout strategies and guide resource allocation in high-risk areas.
The Rhabdoviridae family comprises a diverse range of negative-sense single-stranded ribonucleic acid (RNA) viruses, including significant human and mammalian viruses transmitted by various arthropod species. Herein, using Aedes albopictus (Ae. albopictus) samples collected in two urban parks during 2023 and 2024, through metagenomics sequencing, 16 sequences were identified as putative novel viruses, showing closest homology to insect-specific viruses, mycoviruses, or plant-associated viruses. Notably, two novel viruses, Aedes albopictus almendravirus GCCDC15 (Aealb-AlmV GCCDC15) and Aedes albopictus almendravirus GCCDC16 (Aealb-AlmV GCCDC16) were identified and successfully isolated. Both of these viruses belong to the genus Almendravirus within the Rhabdoviridae family. Phylogenetic analysis revealed that Aealb-AlmV GCCDC15 and GCCDC16 are distantly related to Coot Bay virus (the United States of America, 2013) and Menghai rhabdovirus (Yunnan Province, China, 2017). The genetic distances between these two viruses and their most similar viruses are marked by 59.85 % and 87.20 % of amino acid identity in the L protein, respectively, supporting their classification as two new species in the Rhabdoviridae family. Cytopathic effects and rod-like virions were observed in mosquito cells (C6/36) after inoculating with supernatants from the Ae. albopictus samples. To investigate the natural distribution and persistence of the novel almendraviruses, we conducted a specific reverse transcription-polymerase chain reaction (RT-PCR) screening of Ae. albopictus mosquitoes collected from two urban parks across different time points. The assays confirmed the presence of both Aealb-AlmV GCCDC15 and GCCDC16 in mosquito populations. Critically, these viruses were detected repeatedly over successive sampling periods and in mosquitoes from geographically distinct sites within the urban environment. In summary, our study delineates the virome characteristics of Aedes mosquitoes in the urban ecosystem and successfully isolated two novel rhabdoviruses. The recurrent detection provides clear evidence for the sustained circulation of Ae. albopictus-derived almendraviruses in urban parks, highlighting their ongoing transmission and establishment in these habitats.
At the BIOHK2024, held on September 11–14, 2024, the roundtable discussion titled “Time is now: Preparing for the next pandemic,” brought together Professors Jun Liu, George Fu Gao, Kwok-Yung Yuen, Lit Man Leo Poon, and Nan Song. They explored the current state of global readiness for impending viral threats, focusing on the necessity for enhanced surveillance, improved diagnostic technologies, and the development of more efficient vaccines and drugs. The panel underscored the importance of a coordinated global response, the role of vaccination in mitigating pandemic impacts, and the challenges posed by emerging viruses and their variants. They also highlighted the potential of artificial intelligence in disease prediction and basic researches, and also the need for continuous investment in pandemic preparedness to address the gaps exposed by the coronavirus disease 2019 (COVID-19) pandemic. The discussion concluded on a note of cautious optimism, emphasizing the importance of learning from past experiences and the resilience demonstrated by many countries during the recent pandemic.
This work is aimed at the preparation of complexes of chitosan and hydrophobically modified (HM) chitosan with an anionic surfactant sodium dodecylbenzene sulfonate (SDBS), and at the study of the virucidal activity of the complexes and their components against SARS-CoV-2. It is shown that the introduction of a sufficient amount (4 mol%) of hydrophobic n-dodecyl side groups provides the activity of HM chitosan against SARS-CoV-2 at moderate concentrations, at which unmodified chitosan and chitosan containing a lower amount of hydrophobic groups do not show any activity. Complexes of HM chitosan with SDBS are prepared, which is proven by fluorescence spectroscopy and isothermal titration calorimetry. It is discovered that HM chitosan/SDBS complex is more active than the polymer without surfactant, and an increase of the amount of hydrophobic groups enhances the activity.
The emerging viruses within the genus Henipavirus in the family Paramyxoviridae pose a great threat to public biosafety. To develop a quadruple real-time fluorescence-based quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay is pivotal for the early warning of the potential of zoonotic infectious diseases. Specific primers and probes were designed for the relatively conserved regions based on whole genome sequences of Langya virus (LayV), Mojiang virus (MojV), Nipah virus (NiV), and Cedar virus (CedV), followed by the establishment of a quadruple real-time fluorescence-based qRT-PCR detection method. No cross-reactivity was observed with other viral nucleic acids. The optimal linear detection range for LayV, MojV, NiV, and CedV was 101-108 copies/μL, and the lower limit of detection was 10 copies/μL. Three different DNA concentrations of LayV, MojV, NiV, and CedV (104, 105, and 106 copies/μL) were tested 14 times, achieving good repeatability. The standard deviation of the cycle threshold values for each concentration was <0.5 and the coefficient of variation was <3 %. Furthermore, the amplification efficiency of quadruple real-time fluorescence-based qRT-PCR was >90 %, and the correlation coefficient was >0.99. The established quadruple real-time fluorescence-based qRT-PCR assay for the detection of LayV, MojV, NiV, and CedV exhibits good sensitivity, specificity, and repeatability. Therefore, it can be used to detect Henipavirus and other related clinical specimens.
ABSTRACT Zika virus (ZIKV) infection caused neurological complications and male infertility, leading to the accumulation of antigen-specific immune cells in immune-privileged organs (IPOs). Thus, it is important to understand the immunological responses to ZIKV in IPOs. We extensively investigated the ZIKV-specific T cell immunity in IPOs in Ifnar1 −/− mice, based on an immunodominant epitope E 294-302 tetramer. The distinct kinetics and functions of virus-specific CD8 + T cells infiltrated into different IPOs were characterized, with late elevation in the brain and spinal cord. Single epitope E 294-302 -specific T cells can account for 20-60% of the total CD8 + T cells in the brain, spinal cord, and testicle and persist for at least 90 days in the brain and spinal cord. The E 294-302 -specific TCRαβs within the IPOs are featured with the majority of clonotypes utilizing TRAV9N-3 paired with diverse TRBV chains, but with distinct αβ paired clonotypes in 7 and 30 days post-infection. Specific chemokine receptors, Ccr2 and Ccr5 , were selectively expressed in the E 294-302 -specific CD8 + T cells within the brain and testicle, indicating an IPO-oriented migration of virus-specific CD8 + T cells after infection. Overall, this study adds to the understanding of virus-specific CD8 + T cell responses for controlling and clearing ZIKV infection in IPOs. IMPORTANCE The immune-privileged organs (IPOs), such as the central nervous system and testicles, presented pathogenicity and inflammation after Zika virus (ZIKV) infection with infiltrated CD8 + T cells. Our data show that CD8 + T cells keep up with virus increases and decreases in immune-privileged organs. Furthermore, our study provides the first ex vivo comparative analyses of the composition and diversity related to TCRα/β clonotypes across anatomical sites and ZIKV infection phases. We show that the vast majority of TCRα/β clonotypes in tissues utilize TRAV9N-3 with conservation. Specific chemokine expression, including Ccr2 and Ccr5 , was found to be selectively expressed in the E 294-302 -specific CD8 + T cells within the brain and testicle, indicating an IPO-oriented migration of the virus-specific CD8 + T cells after the infection. Our study adds insights into the anti-viral immunological characterization and chemotaxis mechanism of virus-specific CD8 + T cells after ZIKV infection in different IPOs.
Seasonal flu, primarily caused by influenza A H1N1 and H3N2 subtype viruses or influenza B viruses, is the most prevalent respiratory tract infection globally and leads to substantial morbidity and mortality annually. Despite the influenza virus being initially recognized as a respiratory pathogen with well-characterized transmission through respiratory droplets, its impact on the ocular epithelium and associated gene expression remains relatively unexplored. In this study, we investigated the transcriptional profiles of immortalized human corneal epithelial cells (HCE-S) and A549 human lung epithelial cells infected with H1N1 and H3N2 influenza virus. In comparison with A549 cells, a reduced number of differentially expressed genes was observed in HCE-S upon influenza virus infection. Specifically, there was a significant upregulation of the genes IFI44L and OAS1, along with lower release of the CCL5/RANTES protein. Notably, our findings revealed uniquely upregulated LGALS9 (encoding galectin-9) in HCE-S following infection with the 2009 pandemic H1N1 virus. Furthermore, targeted knockdown of LGALS9 in these cells resulted in a measurable decrease in viral infection, highlighting its role in the cellular responses to influenza virus and suggesting a novel avenue for antiviral therapy. Overall, our findings provide insight into the distinct mechanisms of influenza virus interactions with different epithelial cells and underscore the importance of studying the ocular surface in understanding influenza pathogenesis.