Pseudorabies virus (PRV) is a major etiological agent of swine infectious diseases and is responsible for significant economic losses in the swine industry. Recent data points to human viral encephalitis caused by PRV infection, suggesting that PRV may be able to overcome the species barrier to infect humans. To date, there is no available therapeutic for PRV infection. Here, we report the near-atomic structures of the PRV A-capsid and C-capsid, and illustrate the interaction that occurs between these subunits. We show that the C-capsid portal complex is decorated with capsid-associated tegument complexes. The PRV capsid structure is highly reminiscent of other α-herpesviruses, with some additional structural features of β- and γ-herpesviruses. These results illustrate the structure of the PRV capsid and elucidate the underlying assembly mechanism at the molecular level. This knowledge may be useful for the development of oncolytic agents or specific therapeutics against this arm of the herpesvirus family.

Background: Oncolytic viruses are now well recognized as potential immunotherapeutic agents against cancer. However, the first FDA-approved oncolytic herpes simplex virus 1 (HSV-1), T-VEC, showed limited benefits in some patients in clinical trials. Thus, the identification of novel oncolytic viruses that can strengthen oncolytic virus therapy is warranted. Here, we identified a live-attenuated swine pseudorabies virus (PRV-LAV) as a promising oncolytic agent with broad-spectrum antitumor activity in vitro and in vivo. Methods: PRV cytotoxicity against tumor cells and normal cells was tested in vitro using a CCK8 cell viability assay. A cell kinase inhibitor library was used to screen for key targets that affect the proliferation of PRV-LAV. The potential therapeutic efficacy of PRV-LAV was tested against syngeneic tumors in immunocompetent mice, and against subcutaneous xenografts of human cancer cell lines in nude mice. Cytometry by time of flight (CyTOF) and flow cytometry were used to uncover the immunological mechanism of PRV-LAV treatment in regulating the tumor immune microenvironment. Results: Through various tumor-specific analyses, we show that PRV-LAV infects cancer cells via the NRP1/EGFR signaling pathway, which is commonly overexpressed in cancer. Further, we show that PRV-LAV kills cancer cells by inducing endoplasmic reticulum (ER) stress. Moreover, PRV-LAV is responsible for reprogramming the tumor microenvironment from immunologically naïve (“cold”) to inflamed (“hot”), thereby increasing immune cell infiltration and restoring CD8⁺ T cell function against cancer. When delivered in combination with immune checkpoint inhibitors (ICIs), the anti-tumor response is augmented, suggestive of synergistic activity. Conclusions: PRV-LAV can infect cancer cells via NRP1/EGFR signaling and induce cancer cells apoptosis via ER stress. PRV-LAV treatment also restores CD8⁺ T cell function against cancer. The combination of PRV-LAV and immune checkpoint inhibitors has a significant synergistic effect. Overall, these findings point to PRV-LAV as a serious potential candidate for the treatment of NRP1/EGFR pathway-associated tumors.

Introduction: TORCH is a group of pathogens including Herpes simplex virus (HSV), Cytomegalovirus (CMV), Rubella virus (RV) and Toxoplasma gondii (TOX). Serological screening for the specific antibodies against TORCH pathogens is crucial for preventing fetal malformation and miscarriage. In this study, we analyzed the characteristics of TORCH IgM and IgG seropositivity in reproductive-aged women in Zhangzhou, China. Methods: A total of 1,417 reproductive-aged women prior to conception attended prenatal diagnosis outpatient clinic in Zhangzhou and received the prenatal TORCH serological screening were enrolled in this study. The IgM and IgG antibodies against TORCH pathogens were detected using chemiluminescence immunoassay. Results: The positive rates of IgM for TOX, RV, CMV and HSV-1/2 were 0.64, 2.33, 1.34 and 11.22%. The IgG seropositivity for TOX, RV, CMV, HSV-1 and HSV-2 were 3.81, 72.83, 97.46, 82.64 and 7.27%. The positive rate of HSV-1/2-IgM and TOX-IgG in 2024 were lower than that in 2023. In addition, the positive rates of RV-IgG and HSV-1-IgG were significantly higher in the women aged 30–34 years old and ≥35 years old. The CMV-IgM and HSV-2-IgG positive rates were higher in women ≥35 years old. Regarding seasonal distribution, the positive rate of HSV-1/2-IgM was significantly higher in spring (March to May) than that in winter (December to February). The seropositivity of all TORCH-IgG showed no significant differences across four seasons. Conclusion: Our research highlights the age and seasonal distribution of TORCH seroprevalence in reproductive-aged women in Zhangzhou. These findings underscore that continuous serological surveillance is important for the prevention of congenital infections caused by TORCH pathogens.