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.

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.

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.

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.

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.

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.

Dengue virus (DENV) is a mosquito-borne pathogen responsible for a spectrum of illnesses, including dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Nearly half of the global population is at risk of DENV infection, making it a pressing public health issue worldwide. The limited cross-protection among the four DENV serotypes (DENV1-4) and the phenomenon of antibody-dependent enhancement (ADE) have posed significant challenges to the development of effective dengue vaccines. Furthermore, there are currently no specific antiviral treatments available. This review provides an overview of DENV's key characteristics, clinical manifestations, and recent advancements in antiviral drug development—including the repurposing of approved drugs, peptide-based antiviral agents, therapeutic antibodies, natural products with antiviral potential, and host factor inhibitors—aiming to offer critical insights to inform strategies for managing and preventing dengue outbreaks.

The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.

Mammals are critical reservoirs of human infectious diseases and the spillover of viruses is related to climate conditions. We conducted meta-transcriptomic sequencing of 226 mammals (bats, rodents, hedgehogs, and shrews) representing 20 species collected across eight cities in south China between 2018 and 2024. Samples included internal organs, oropharyngeal and anal swabs, and feces. We identified 63 vertebrate-associated viruses, including 34 novel viruses. Phylogenetic analysis revealed six viruses with potential infection risks to humans or domestic animals due to their close phylogenetic relationships with known pathogens. Cross-species transmission was observed in 14.3% (9/63) of viruses, shared by at least two host species, with bats, particularly Rhinolophus and Hipposideros, serving as key hubs for viral circulation and zoonotic spillover. Virome composition varied substantially among mammalian species and geographic regions (adonis test, R² = 0.50, P = 0.001). Generalized linear models quantified the roles of host taxonomy, ecotypes, and meteorological factors in shaping viral diversity, demonstrating host taxonomy (at the order level) as a predominant role (25.70% deviance explained), followed by ecotypes (10.27% deviance explained). Phylogenetic analysis conducted using our betacoronavirus sequences, as well as betacoronavirus sequences derived from 2.0 × 10⁴ bats sampled in China between July 2013 and March 2024, revealed that no betacoronaviruses exhibited closer phylogenetic relationships to SARS-CoV-2 than the known strains (e.g., RaTG13). These findings provide critical insights into virus evolution, transmission, and ecological determinants, which are essential for the prevention of emerging infectious diseases.

The persistence of covalently closed circular DNA (cccDNA) in hepatitis B virus (HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment. Understanding the molecular mechanisms regulating HBV cccDNA transcription is essential for developing novel therapeutic strategies. In this study, we investigated the role of RNA binding motif protein 25 (RBM25) in HBV replication, focusing on its interaction with cccDNA and its regulation of host transcription factors. The results demonstrated that RBM25 knockdown markedly inhibited HBV replication, reducing levels of HBV DNA, hepatitis B e antigen (HBeAg), hepatitis B surface antigen (HBsAg), HBV RNA, and L-HBs in HBV-replicating and infected cell models. Consistent results were observed in a mouse model hydrodynamically injected with 1.2 × HBV plasmid. Conversely, RBM25 overexpression significantly enhanced HBV replication. Mechanistically, RBM25 promoted HBV promoter activities by binding to cccDNA through its RE/RD and PWI domains. This effect was mediated by increased Yin Yang 1 (YY1) expression, which enhanced acetylation of cccDNA-bound histones, promoting HBV transcription. Furthermore, RBM25 expression was upregulated and translocated to the nucleus following core protein expression and accumulation, while overexpression of RBM25 promoted core protein degradation. In conclusion, this study demonstrates that RBM25 is a novel host factor that enhances HBV replication by upregulating YY1-dependent transcriptional activation of cccDNA. It also reveales a reciprocal regulatory mechanism between the HBV core protein and RBM25, which helps sustain HBV replication.

The cross-species infection of coronaviruses has resulted in several major epidemics since 2003. Porcine epidemic diarrhea virus (PEDV) is a devastating swine enteric coronavirus, which targets pigs as the only natural reservoir. In this study, the nucleic acid of PEDV was detected in rat fecal samples collected from pig farms. Further animal tests showed that PEDV can cause systemic infections in neonatal mice and rats via intracranial inoculation. The brain, lung, intestine and spleen were all targets for PEDV in rodents in contrast to the intestine being targeted in pigs. Morbidity and mortality vary via different infection routes. PEDV was also detectable in feces after infection, suggesting that the infected rodents were potential infectious sources. Moreover, the cerebral tropism of PEDV was verified in piglets via orally inoculation, which had not been identified before. In conclusion, our findings demonstrate that PEDV could cross the species barrier to infect mice and rats through different routes in experimental settings. Although it is highly devastating to piglets, PEDV changes the target organs and turns to be milder when meeting with new hosts. Based on these findings, more attention should be paid to the potential cross-species infection of PEDV.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV), characterized by high fever and thrombocytopenia. It has been proved that traditional Chinese medicine (TCM) has displayed definite therapeutic effects on viral hemorrhagic fever, indicating its potential to treat SFTS. In this study, SFTS-relative key targets were predicted via gene ontology (GO) analysis and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Molecular docking was then used to select stable binders. Molecules matched TCMs were identified, and a new prescription, Qingqi Guxue decoction (QQGX), was formulated to clear heat and nourish blood, with a resulting drug composition network. We explored the optimal drug proportion for QQGX. Through an in-depth study of molecular mechanisms, we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2 (CCNA2) and cyclin-dependent kinase 2 (CDK2), thereby inhibiting SFTSV replication. Finally, we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV. In summary, our study prepared a TCM decoction using the method of network pharmacology. This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.

Zika virus (ZIKV) is a mosquito-borne virus belonging to the genus Orthoflavivirus, and the family Flaviviridae. It commonly presents with febrile-like symptoms, neurological issues, and pregnancy complications in humans. Currently, there is no commercial vaccine or specific treatment available to prevent ZIKV infection. Therefore, controlling the epidemic's spread relies on preventing mosquitoes from transmitting the virus. Although various studies have explored the transmission of ZIKV between mosquitoes and vertebrate hosts, comprehensive research on potential mosquito-to-mosquito transmission of ZIKV remains limited. In this study, we conducted systematic laboratory investigations to assess the ability of ZIKV to spread among mosquitoes, and to evaluate the impact of ZIKV infection on mosquito development. Our findings revealed that ZIKV can be transmitted between Aedes aegypti mosquitoes both vertically and horizontally, through oviposition and contact between mosquitoes of the same or opposite sex. Additionally, we observed that ZIKV infection resulted in a reduction in the number of mosquito eggs but an increase in their size. The widespread distribution of ZIKV in infected mosquitoes and the altered levels of hormone related genes following viral infection were noted, which may contribute to viral transmission among mosquitoes and affect mosquito development. This research provides systematic experimental evidence of ZIKV transmission among mosquitoes, which is crucial for developing novel strategies to disrupt the spread of orthoflaviviruses and other mosquito-borne pathogens.

Respiratory syncytial virus (RSV) is one of the most common viruses leading to lower respiratory tract infections (LRTIs) in children and elderly individuals worldwide. Although significant progress in the prevention and treatment of RSV infection was made in 2023, with two anti-RSV vaccines and one monoclonal antibody approved by the FDA, there is still a lack of postinfection therapeutic drugs in clinical practice, especially for the pediatric population. In recent years, with an increasing understanding of the pathogenic mechanisms of RSV, drugs and drug candidates, have shown great potential for clinical application. In this review, we categorize and discuss promising anti-RSV drug candidates that have been in preclinical or clinical development over the last five years.

Rotavirus infections cause severe gastroenteritis and dehydration in young children and animals worldwide, leading to high rates of morbidity and mortality, predominantly in low- and middle-income countries. In the past decade, substantial progress has been made in the development and implementation of rotavirus vaccines, which have been essential in alleviating the global burden of this disease, not only in human being but also in livestock species like calves and piglets, where these infections can cause significant economic losses. By synthesizing the latest research and real-world evidence, this review article is designated to provide deep insights into the current state of rotavirus vaccine technology and its global implementation as well as the application of rotavirus vaccines in veterinary settings and their importance in controlling zoonotic transmission and maintaining food security.