Influenza A virus (IAV) remains a global public health concern, causing influenza-like illness and severe respiratory tract infections. Two major subtypes, A/pdm09 H1N1 and A/H3N2, circulate globally, and their epidemics are influenced by multiple factors, especially during the COVID-19 pandemic. Based on data from the National Influenza Surveillance Program in China, we analyzed the epidemiological and genomic data in Tianjin collected from 2017 to 2025. A total of 77,473 throat swabs were collected, of which 9144 were IAV-positive. The A/pdm09 H1N1 and A/H3N2 lineages exhibited distinct epidemics across different influenza seasons, with a decline in cases observed during the COVID-19 pandemic. We sequenced the genomes of 128 A/pdm09 H1N1 and 113 A/H3N2 clinical isolates and characterized their temporal evolution and genetic diversity using time-scaled phylogenetic analysis. Additionally, we conducted a genetic risk evaluation of the hemagglutinin and neuraminidase segments, identifying key amino acid residues associated with viral adaptation, transmissibility, virulence, and drug resistance. Moreover, no antigenic variants were found in clinical isolates during the recent influenza seasons, though reduced sensitivity to oseltamivir and zanamivir was observed in individual strains. Our surveillance highlights the epidemiology and evolution of IAV before and after the COVID-19 pandemic in Tianjin.

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.

Human parainfluenza viruses (HPIV) are common viral pathogens in acute respiratory infection (ARI). We aimed to describe the epidemiological and molecular characteristics of HPIV from ARI patients. This cross-sectional study was conducted using respiratory samples from 9,696 ARI patients between 2016 and 2020 in southern China. All samples were analyzed by quantitative real-time polymerase chain reaction to determine the presence of HPIV and other common respiratory viruses. Descriptive statistics were performed to determine the temporal and population distribution of HPIV. The full-length hemagglutinin-neuraminidase (HN) gene of HPIV3-positive samples was sequenced for phylogenetic analysis. A total of 577 (6.0%) patients tested positive for HPIV, with HPIV3 being the predominant serotype, accounting for 46.8% of cases. Notably, 66.0% of these HPIV-positive cases were children aged 0-2 years. The prevalence of HPIV infections showed a decreased trend and altered peak during 2016-2020. Cough, fever, sputum production, and rhinorrhea were common respiratory symptoms in HPIV-positive patients. The majority of cases had pneumonia (63.4%). Human rhinovirus (HRV) and human coronavirus (HCoV) were the most common coinfection viruses in HPIV-positive cases, with proportions of 20.1% and 14.4%, respectively. Phylogenetic analysis revealed that the predominant lineage of HPIV3 was C3f (86.0%), followed by lineage C3a (8.0%), C3d (4.0%), and C3b (2.0%). These findings help to better understand the epidemiology of HPIV, and improve public health strategies to prevent and control HPIV infections in southern China.

Porcine reproductive and respiratory syndrome (PRRS), a highly infectious immunosuppressive disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), has led to significant economic losses in the global swine industry. The complexity of preventing and controlling PRRS, compounded by the limited efficacy of current vaccines, underscores the urgent need to identify antiviral targets and develop effective therapeutics against PRRSV. From the perspective of virus-host interactions, the discovery of target molecules associated with PRRSV resistance offers a promising strategy for future disease management. In this study, we conduct a comprehensive proteomic analysis using data-independent acquisition (DIA) mode to investigate the host response throughout the acute phase of PRRSV infection. This approach provides critical insights into the regulation of host antiviral and immune pathways during acute infection, advancing our theoretical understanding of PRRSV-host interactions and host gene dynamics during this critical phase. Notably, we identified SCARB2, a major lysosomal membrane protein associated with cholesterol metabolism, as a potential regulator of PRRSV replication. These findings offer novel perspectives for the prevention and control of PRRSV, contributing to the development of targeted antiviral strategies.

Artemisia annua L. is a medicinal herb with multiple therapeutic applications, whereas its anti-influenza A virus (IAV) efficiency and mechanism of action are still unclear. Here, we investigated the inhibition activity and mechanism of A. annua leaf methanol extracts (AALME) against IAV in vitro and in vivo. Our results revealed that AALME exhibits potent anti-IAV activity by interacting with IAV particles. Mechanistically, AALME directly targets the IAV nucleoprotein (NP) protein and abolishes the nuclear import of IAV NP. AALME profoundly suppresses IAV-induced mitochondrial apoptosis via suppressing ROS-mediated AIF-dependent pathways. More importantly, we found that AALME plays a crucial role in protecting mice from IAV infection and mitigating IAV pathogenicity. This current work provides mechanistic insight into the mechanism by which AALME controls IAV infection in vitro and in vivo, potentially contributing to the development of antiviral treatments for IAV infection.

As an emerging genotype, the G9 genotype rotaviruses (RVs) are widespread among humans and pigs, and have been reported in many countries and regions in the recent years. Moreover, porcine G9 strains could cross the interspecies barrier to infect human. To investigate the epidemic trends of porcine G9 strains as well as the cross-immunoreactivity among different isolates, an epidemiological investigation about porcine G9 genotype RVs (PoRVs) was performed during the period 2020-2023 in multiple provinces of China. A total of nine representative strains were identified. The phylogenetic analysis based on viral VP7 gene showed that these strains mainly clustered with lineages III and VI, which revealed the predominant G9 PoRVs in China. Moreover, a new lineage, lineage VII, was identified, and strains of this lineage were found to be circulating in Guangdong and Taiwan. Except lineages I and IV, some isolates from other lineages could co-circulate in pigs and humans. Three G9 strains, namely 923H, 923E, and 923X, which belonged to the largest sub-lineage III, were isolated. Then, the significant cross-reactivity was observed among strains of the same or different lineages. This study is the first to systematically investigate the genetic and immunogenetic characteristics of porcine G9 genotype rotavirus in China, as well as the potential cross-species transmission between pigs and humans, providing a valuable direction for the effective prevention of porcine rotavirus.

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.

On January 30, 2024, China announced the first human case of H10N5 influenza infection. Prior to this, human cases of H10N7 and H10N8 had been reported. It is now appropriate to re-examine the evolution and future epidemiological trends of the H10 and N5 subtypes of avian influenza viruses (AIVs). In this study, we analyzed the reassortment characteristics of the first human-derived H10N5 AIV (A/Zhejiang/ZJU01/2023), as well as the evolutionary dynamics of the wild bird-derived H10 and N5 subtypes of AIVs over the past decade. Our findings indicate that the human-derived H10N5 AIV exhibited low pathogenicity. A/bean_goose/Korea/KNU-10/2022(H10N7) and A/mallard/Novosibirsk_region/962k/2018(H12N5) were identified as the potential reassortment parents. The virus has existed since 2022 and several isolations have been reported in Bangladesh. Phylogenetic analysis showed that H10Ny and HxN5 AIVs in China are clustered differently based on the East Asian-Australian (eastern) and Central Asian-Indian (western) migratory flyways. The H10Ny and HxN5 AIV reassortant strains may cause human infections through accidental spillover. It is possible that another center of AIV evolution, mutation, and reassortment may be developing along the migratory flyways in northeastern Asia, distinct from Europe, the Americas, and China's Yangtze River Delta and Pearl River Delta, which should be closely monitored to ensure the safety of the public.

The H9N2 subtype avian influenza virus (AIV) continues to propagate and undergo evolution within China, thereby posing a significant threat to the poultry industry. This study encompassed the collection of 436 samples and swabs in East China over the period spanning 2018 to 2019, from which 31 strains of the H9N2 subtype viruses were isolated and purified. We revealed that the HA and NA genes of the 31 isolates categorized within the Y280 branch, while the PB2 and M genes were associated with the G1 branch, and the remaining genes aligned with the F/98 branch. Despite this alignment, antigenic mapping demonstrated differences between the 2018 and 2019 strains, with the early vaccine strains displaying low serological reactivity toward these isolates. Notably, the CK/SH/49/19 isolate exhibited lethality in mice, characterized by a PB2 E627V mutation and a HA deletion at amino acid position 217. Mechanistically, in vitro studies showed that the influenza virus CK/SH/49/19 carrying PB2 627V and HA 217M mutations displayed enhanced replication capacity, attributed to the heightened activity of the polymerase with PB2 627V. Moreover, the absence of the amino acid at the HA 217 site obstructed viral adsorption and internalization, resulted in lower activation pH, and impeded the virus budding process. Critically, in vivo experiments revealed that CK/SH/49/19 (PB2 627V, HA 217Δ) triggered a robust activation of interferon response and interferon-stimulated genes. This study furnished a theoretical foundation for the scientific prevention and control strategies against H9N2 subtype avian influenza.

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.