Human interferon-alpha (IFN-α) includes 13 subtypes, but only IFN-α2 (a/b) is clinically approved for chronic hepatitis B (CHB) therapy, limited by adverse effects and suboptimal response rates. Previously, we identified IFN-α14 as a superior anti-HBV subtype compared to IFN-α2, leading to the engineering of the IFN-α2-EIFK variant, which mimics IFN-α14's enhanced antiviral activity through targeted mutations at receptor-binding sites. However, the in vivo anti-HBV effects of IFN-α2-EIFK remained unexplored due to its short plasma half-life and lack of immunocompetent murine systems suitable for evaluating human IFN-α activity. Using an immunocompetent IFNAR-hEC mouse model and HBV-infected human-liver chimeric mice etc, we demonstrated that N-terminally PEGylated IFN-α2-EIFK (PEG-IFN-α2-EIFK) suppressed HBV replication and antigen expression approximately 10-fold more effectively than PEG-IFN-α2 at equivalent mass doses, while concurrently activating IFN-γ-like signaling pathways in both hepatocytes and immune cells. Subsequent single-cell analysis of intrahepatic immune cells from IFNAR-hEC mice showed that PEG-IFN-α2-EIFK was associated with enhanced antigen-presenting capacity of macrophages, dendritic cells (DCs), and B cells. In addition, PEG-IFN-α2-EIFK was found to preferentially promote M1-like macrophage polarization, and modulate PD-L1/PD-1 interactions between macrophages and CD8+ T cells, accompanied by attenuation of an exhaustion-associated CD8+ T cell state. In conclusion, this study demonstrates that PEG-IFN-α2-EIFK exhibits greater anti-HBV activity and immunomodulatory potency than PEG-IFN-α2 under equivalent mass dosing, supporting its potential as an enhanced therapeutic candidate for CHB.
Listeriosis is an uncommon but severe foodborne infection, yet nationwide data linking pathogen genomics with clinical manifestations remain limited. We analyzed 1,252 laboratory-confirmed symptomatic listeriosis cases reported through nationwide surveillance in Taiwan during 2018–2025, with whole-genome sequencing of the corresponding clinical Listeria monocytogenes isolate from every case. The average annual incidence was 6.68 cases per 1,000,000 person-years, and 30-day all-cause mortality was 11.4%. Incidence showed an age-dependent sex pattern, with higher incidence among females aged 15–44 years and a shift toward male predominance at older ages. The female excess at ages 15–44 years persisted after exclusion of documented maternal–neonatal cases (male-to-female incidence rate ratio, 0.57; 95% confidence interval, 0.36–0.89). Clonal complex 87 (CC87) was the predominant CC (35.9%), whereas CC1 and CC2 were associated with higher odds of central nervous system (CNS) infection. LIPI-4 occurred predominantly in CC87, and LIPI-4-positive isolates showed lower odds of CNS infection; however, this association could not be separated from clonal background. More broadly, most associations of pathogenicity islands, virulence genes, and their alleles with disease manifestations could not be separated from the underlying clonal backgrounds in which these markers occurred, and none of the estimable associations remained significant after CC adjustment. This nationwide clinical–genomic study characterizes the contemporary burden of listeriosis in Taiwan and highlights clonal background as essential context for interpreting associations between virulence markers and disease manifestations.
Clade 2.3.4.4b H5 viruses have undergone continuous evolution since their emergence in China, but the extent of genetic and antigenic diversification among recently circulating viruses remains unclear. Here, we characterised 18 H5 viruses isolated through routine surveillance in China during 2024-2025, together with publicly available clade 2.3.4.4b H5 sequences collected since 2020. Phylogenetic analysis revealed that these isolates formed a distinct evolutionary cluster within clade 2.3.4.4b, designated the G2-derived emerging cluster (G2-EC), which emerged around mid-2024 and exhibited clear genetic divergence from previously circulating H5N1 viruses. G2-EC viruses accumulated a characteristic set of hemagglutinin amino acid substitutions, most of which were located in antigenic regions. Across the clade 2.3.4.4b H5 virus population, the estimated mean HA evolutionary rate was higher during 2024-2025 than during preceding periods. These genetic changes were accompanied by marked antigenic divergence from the Re14 vaccine strain, with 4- to 32-fold reductions in HI titres. Genomic analysis revealed acquisition of PB1 segment from a distinct genetic background in G2-EC H5N1 viruses, followed by the emergence of H5N6 viruses sharing a highly similar genetic backbone but carrying a distinct NA segment, indicating sequential reassortment. Animal experiments showed that representative G2-EC viruses retained high pathogenicity and efficient direct-contact transmission in SPF chickens, while exhibiting relatively limited lethality in mice. Collectively, these findings document a recent evolutionary transition of clade 2.3.4.4b H5 viruses in China, characterised by genetic and antigenic divergence accompanied by sequential reassortment, underscoring the need for continued genomic and antigenic surveillance.
Objectives This study aimed to assess the positivity rate, disease burden, and complications of rotavirus gastroenteritis (RVGE) among Chinese children under 14 years of age presenting with acute gastroenteritis (AGE).Methods A multicentre, observational, and retrospective study was conducted at 11 centres across China (July 2013 - June 2023). Data on RVGE prevalence, direct medical costs, and complications were analyzed, with projections of direct economic burden for 2025 - 2034.Results Out of 505,987 AGE visits, the rotavirus positivity rate was 15.70%, peaked at 26.41% in the 12-month period from July 2016 to June 2017, and the annual positivity rate declined by 19.63% between 2017 and 2023. Among 7,113 RVGE cases, 28.57% of inpatients had recorded complications, and the estimated rate of recorded complications among all RVGE patients was 8.29%, most commonly recorded complications being myocardial damage, dehydration, respiratory infection, convulsion, and metabolic acidosis. The median cost of RVGE was CNY 272.80 (USD 40.68) for outpatients and CNY 5336.60 (USD 795.69) for inpatients, respectively. Projected economic burden is estimated to decrease from CNY 8.55 billion (USD 1.21 billion) in 2025 to CNY 3.96 billion (USD 559 million) in 2034.Conclusions RVGE was associated with high complication rates. The decrease in rotavirus prevalence since 2018, highlighting the public health value of a series of preventive measures during this period, including vaccination.
