Virologica Sinica最新文献

Due to inherent immune deficiency, the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune responses in people living with HIV (PLWH) following breakthrough infection with remain incompletely elucidated. A large-sample real-world study was conducted from December 2022 to January 2023, which systematically analyzed immune responses in 1367 PLWH and 219 people without HIV (PWOH) by evaluating serum IgG antibody levels against SARS-CoV-2 wild-type strain and Omicron variants, neutralizing antibody titers, as well as the features of SARS-CoV-2-specific T-cell responses in this population. The results demonstrated that the breakthrough Omicron infection rate in PLWH (60.6%) was significantly lower than that in PWOH. Meanwhile, PLWH exhibited notably reduced IgG antibody levels against both the wild-type strain and Omicron BF.7 variant, with a concurrent decline in neutralizing antibody titers. However, fully vaccinated PLWH with CD4⁺ T-cell counts ≥200 cells/μL achieved post-infection antibody levels comparable to those of PWOH. Notably, PLWH with CD4⁺ T-cell counts <200 cells/μL or unvaccinated PLWH showed obvious impairment in both humoral and cellular immunity. Although PLWH could maintain relatively high levels of SARS-CoV-2-specific antibodies and T-cell responses within six months after infection, the overall intensity of their immune responses remained lower than that of PWOH. Furthermore, while wild-type SARS-CoV-2 vaccines could effectively elevate antibody levels in PLWH, their protective efficacy against Omicron variants was relatively limited. These findings provide important experimental and clinical evidence for formulating exclusive and targeted SARS-CoV-2 vaccination strategies for PLWH.

Sp100 (Speckled protein 100 kDa), a key component of promyelocytic leukemia (PML) nuclear bodies, plays a pivotal role in intrinsic and innate immunity. The predominant isoform, Sp100A, has been shown by our previous studies to shuttle between subcellular compartments to enhance innate immunity against RNA viruses and to circulate between cells via extracellular vesicles (EVs) to restrict herpes simplex virus 1 (HSV-1) spread. This study investigates the biological significance of the cyto-nuclear shuttling of Sp100A, a key component of PML nuclear bodies, in antiviral defense against DNA viruses, particularly herpes simplex virus 1 (HSV-1). We demonstrate that Sp100A effectively inhibits multiple DNA viruses in vitro, with its antiviral activity being critically regulated by phosphorylation at the S188 site (a nuclear import-mimicking mutant, S188D, is active, while the S188A mutant is not). Furthermore, DNA virus infection and type I IFN significantly induce Sp100A secretion via extracellular vesicles (EVs), which confers broad, non-IFN-mediated antiviral protection between cells. In a murine model, Sp100A expression significantly reduced HSV-1 lytic replication and clinical signs, but did not impair latency establishment or reactivation potential. These findings underscore the critical role of Sp100A's dynamic shuttling in antiviral defense, showing its activity is specifically restricted to the lytic phase of HSV-1. Sp100A's multifaceted antiviral properties highlight its potential as a novel therapeutic target for combating DNA virus infections.

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.

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.

With recent advances in synthetic biology methods, the genomes of several large DNA viruses have been de novo synthesized and assembled, leading to the functional rescue of the respective viruses. Pseudorabies virus (PRV), a large DNA virus belonging to the family Herpesviridae, causes severe diseases in swine, resulting in significant economic losses to the global pig farming industry. Genome editing is crucial for attenuating virulence and developing safer vaccines for PRV. However, its complex repetitive sequences and extremely high GC-rich genome pose significant challenges for genetic manipulation. In this study, we developed a PRV genome assembly platform using yeast-based transformation-associated recombination (TAR) technology. The genome of a prevalent genotype II variant strain, PRV-GX-2011 (GenBank number PV405324.1), was divided into nine A-level fragments and cloned into vectors via TAR. Subsequently, three B-level fragments were generated by recombining three A-level fragments each. In vitro CRISPR/Cas9-mediated editing was introduced to insert an egfp gene into the non-coding intergenic region between UL23 and UL22 genes. Infectious viruses were rescued by co-transfection of linearized B-level fragments in Vero cells, and an isolated virus, PRV-GX-Syn1, was purified via plaque assay. While PRV-GX-Syn1 exhibited reduced viral titer and smaller plaque size compared to the parental strain, its morphological characteristics remained indistinguishable from the parental virus. In BALB/c mice, PRV-GX-Syn1 caused lethal infection, producing lung pathology comparable to the parental strain. This TAR-based platform offers faster and more flexible genomic modification of PRV, facilitating both basic research and PRV-based vaccine vectors.

Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affects multiple organ systems, with the respiratory system being the primary target. Respiratory organoids, which closely mimic the structure and function of the human respiratory tract, have emerged as essential tools for studying SARS-CoV-2 infection. This review summarizes current methods for generating various respiratory organoids, including nasal, tonsil, airway, bronchial, and alveolar organoids, and highlights their application in investigating the mechanism of SARS-CoV-2 infection and evaluating potential therapeutic agents. Meanwhile, this review also introduces respiratory organoid-on-a-chip technology, which can precisely regulate culture conditions and incorporate vascularization and immune cells to enhance physiological complexity, thereby providing crucial support for investigating SARS-CoV-2-induced lung injury, immune responses, and conducting high-throughput drug screening. The aim of this review is to provide valuable insights for further research into the pathogenesis and intervention strategies of COVID-19.

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.