Virologica Sinica最新文献

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 Δ34.5Δ47) 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 Δ34.5Δ47-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 Δ34.5Δ47 as a safe and versatile platform for both HSV-1 prophylaxis and heterologous antigen delivery.

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.

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.

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.

Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo hemorrhagic fever virus (CCHFV), is endemic in Africa, Asia, and Europe. However, CCHF epidemiology and epizootiology have been poorly defined in Europe. Here, we summarize the current knowledge of CCHFV distribution in (non-Russian) Europe, including countries previously not considered to be at risk. We collected data on CCHF cases, human/vertebrate animal anti-CCHFV seroprevalence, CCHFV vector (Hyalomma tick), and CCHFV isolation from ticks and classified countries into five risk levels using a One Health approach. From 1944 through Feb 2025, more than 2,000 recorded CCHF cases were identified in Europe, mostly from southern/eastern countries/regions, primarily Bulgaria (at least 1,623), Kosovo (at least 339), Ukraine (at least 336), Croatia (at least 200), Albania (at least 146), and Republic of Moldova (at least 60). Albania, Bulgaria, Greece, Kosovo, and Spain were categorized as level 1 (reported CCHF cases, presence of robust surveillance systems). North Macedonia, Portugal, and Ukraine/Crimea were assigned to level 2 (reported CCHF cases in the absence of robust established surveillance). Bosnia and Herzegovina, Croatia, France, Hungary, Italy, Montenegro, Republic of Moldova, Romania, and Slovenia were assigned to level 3 due to evidence of CCHFV circulation in absence of recent CCHF cases. Thirty-four countries were assigned to level 4 (presence of Hyalomma ticks) or level 5 (no data). This work provides information on CCHFV distribution and burden with list of at-risk areas to inform international and local public health agencies to establish or strengthen surveillance systems.

Entomopathogenic viruses, such as baculoviruses and cypoviruses, have been employed as biological pesticides against agricultural and forestry pests. However, their susceptibility to inactivation under field UV radiation has hindered their broader application. In this study, we effectively improved the UV resistance of insect virus occlusion bodies (OBs) by coating their surfaces with silica nanoparticles (SiO₂ NPs). Monodisperse SiO₂ NPs with uniform size distribution and excellent colloidal stability were synthesized using the Stöber method. Subsequent amination modification of the SiO₂ NPs with a silane coupling agent shifted their isoelectric point from 3.2 to 8.1. This modification imparted a strong positive charge to the NPs within the pH range of 4.5-5.5, while the OBs of insect viruses remained negatively charged in this range. Consequently, the amino-functionalized SiO₂ NPs were successfully coated onto the surfaces of OBs of three representative insect viruses: nucleopolyhedrovirus, granulovirus, and cypovirus, through electrostatic interactions. Laboratory bioassays confirmed that Mamestra brassicae multiple nucleopolyhedrovirus (MbMNPV) coated with SiO₂-NH₂ NPs retained its native viral pathogenicity against Spodoptera exigua larvae under normal laboratory condition, while it demonstrated 2.299-2.712 folds higher potency than MbMNPV physically mixed with unmodified SiO₂ NPs after UV irradiation. Outdoor trials revealed that SiO₂-NH₂ NPs coating significantly improved the survival time of MbMNPV, with the median survival time increased from 1.43 days to 5.15 days. This nanoparticle coating strategy establishes a robust platform for developing photostable biopesticides while preserving their ecological safety profiles. The modular nature of this approach suggests its broad applicability across different entomopathogenic virus formulations.