Transboundary and Emerging Diseases
·
2024
·Vol. 2024
·期 1
·5929976
·
IF 3.5
Xue Li,Nan Li,Jiawei Zheng,Xinru Lv,Yaqi Han,Huimin Zhang,Ying Ren,Gefen Yin,Linzhu Ren
Pseudorabies virus (PRV) is widely spread, characterized by high contagiousness, high viral load, and strong infectivity, and poses severe threats to the global pig farming industry. Apart from pigs, PRV can also infect several other mammals, including mice, cattle, cats, dogs, and wolves, with diverse clinical symptoms. Notably, approximately more than 20 cases of human PRV infection have been reported in recent years, with fever, seizures, human encephalitis, intraocular inflammation, and severe central nervous system symptoms. However, whether PRV can infect humans or belongs to a zoonotic virus is still controversial. In this study, human neuronal cells were infected with PRV and blindly passaged to obtain human cell-adapted PRV, followed by comparing the characteristics of human cell-adapted PRV and pig-derived PRV in vitro and in vivo , to determine whether PRV has the potential to infect humans. The results showed that PRV could be stably passaged in human cells and produced progeny viruses similar to the parental virus, including morphology, infectivity, and pathogenicity. The human cell-adapted PRV can also cross-transmit to cells from other origins, including humans, mice, pigs, and monkeys, causing different cytopathic effects. Moreover, multiple tissue damage can be detected in mice infected with human cell-adapted PRV. These results demonstrate that PRV is a potential zoonotic virus, and it is necessary to pay close attention to the spread and variation of the virus in animals and humans.
研究领域:
病毒学
·
人畜共患病
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
高影响因子
Journal of Saudi Chemical Society
·
2025
·Vol. 29
·期 4
·1-17
·
IF 5.8
Xing Jiayou,Yao Chen,Xu Yingna,Yang Guoyu,Shi Lijun
Compounds containing a 1,3,5-triazine skeleton exhibit broad-spectrum biological activity, particularly in the fields of antiviral, antibacterial, anticancer, and anti-inflammatory properties in medicine. In this study, a series of 1,3,5-triazine derivatives containing morpholine group were designed and synthesized. Their structures were identified by 1 H NMR, 13 C NMR, HRMS and X-ray single crystal diffraction, and their antiviral activity against pseudorabies virus (PRV) and vesicular stomatitis virus (VSV) was evaluated. The results of cell-based assays revealed that some target compounds possessed excellent antiviral effect against PRV and VSV. Compounds 10ce (SI: 30.82 against PRV, 16.19 against VSV) and 10de (SI: 10.26 against PRV, 13.22 against VSV) exhibited excellent antiviral activity, with significantly higher selectivity indices compared to other derivatives. Further investigations revealed that both compounds effectively inhibited the viral progeny titers of both PRV and VSV. This antiviral activity was corroborated by Western blot and qRT-PCR analyses, which demonstrated significant downregulation of the corresponding viral proteins and their associated genes. Molecular docking studies demonstrated that compounds 10ce and 10de bound to the active site of PIKfyve with binding energies of -11.2 kcal/mol and -11.4 kcal/mol, respectively, forming hydrogen bonds and hydrophobic interactions. These findings suggest that their antiviral effects may be mediated through interactions with PIKfyve. Moreover, cytotoxicity assays showed that the CC50 values of compounds 10ce and 10de were 47.77 μM and 46.39 μM, respectively, indicating their relatively high safety profiles. These results suggest that 1,3,5-triazine-based compounds are highly promising candidate drugs worthy of further development.
研究领域:
药物化学
·
病毒学
·
药理学
·
化学生物学
·
结构生物学
✓ 已验证
DOI
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Lu Chenhe,Li Haimin,Chen Wenjing,Li Hui,Ma Jiayu,Peng Peng,Yan Yan,Dong Weiren,Jin Yulan,Pan Shiyue,Shang Shaobin,Gu Jinyan,Zhou Jiyong
Introduction: Variant pseudorabies virus (PRV) is a newly emerged zoonotic pathogen that can cause human blindness. PRV can take advantage of its large genome and multiple non-essential genes to construct recombinant attenuated vaccines carrying foreign genes. However, a major problem is that the foreign genes in recombinant PRV are only integrated into the genome for independent expression, rather than assembled on the surface of virion.Methods: We reported a recombinant PRV with deleted gE/TK genes and an inserted porcine circovirus virus 2 (PCV2) Cap gene into the extracellular domain of the PRV gE gene using the Cre-loxP recombinant system combined with the CRISPR-Cas9 gene editing system. This recombinant PRV (PRV-Cap), with the envelope-embedded Cap protein, exhibits a similar replication ability to its parental virus.Results: An immunogenicity assay revealed that PRV-Cap immunized mice have 100% resistance to lethal PRV and PCV2 attacks. Neutralization antibody and ELISPOT detections indicated that PRV-Cap can enhance neutralizing antibodies to PRV and produce IFN-γ secreting T cells specific for both PRV and PCV2. Immunological mechanistic investigation revealed that initial immunization with PRV-Cap stimulates significantly early activation and expansion of CD69+ T cells, promoting the activation of CD4 Tfh cell dependent germinal B cells and producing effectively specific effector memory T and B cells. Booster immunization with PRV-Cap recalled the activation of PRV-specific IFN-γ+IL-2+CD4+ T cells and IFN-γ+TNF-α+CD8+ T cells, as well as PCV2-specific IFN-γ+TNF-α+CD8+ T cells.Conclusion: Collectively, our data suggested an immunological mechanism in that the recombinant PRV with envelope-assembled PCV2 Cap protein can serve as an excellent vaccine candidate for combined immunity against PRV and PCV2, and provided a cost-effective method for the production of PRV- PCV2 vaccine.
研究领域:
病毒学
·
免疫学
·
分子生物学
·
疫苗开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Anan Guo,Lvqing Tang,Bing Yang,Niling Xie,Yandong Cui,Wen Sun,Yuan Li,Xiangting Li,Yang Wu,Yingshuai Liu
Adjuvants including aluminum adjuvant (Alum) and oil-water emulsion have been widely used in inactivated pseudorabies virus (PRV) vaccines to improve their performance, however, they are not sufficient to protect from PRV infection because of the weak immune response and poor Th1-type immune response. Divalent manganese ion (Mn 2+ ) has been reported to increase the cellular immune response significantly. In this work, a xanthan gum and carbomer-dispersed Mn 2+ -loaded tannic acid-polyethylene glycol (TPMnXC) nanoparticle colloid is developed and used as an adjuvant to improve the performance of the inactivated PRV vaccine. The good in vitro and in vivo biocompatibility of the developed TPMnXC colloid has been confirmed by the cell viability assay, erythrocyte hemolysis, blood routine analysis, and histological analysis of mouse organs and injection site. The TPMnXC-adjuvanted inactivated PRV vaccine (TPMnXC@PRV) significantly promotes higher and more balanced immune responses indicating with an increased specific total IgG antibody and IgG2a/IgG1 ratio, efficient splenocytes proliferation, and elevated Th1- and Th2-type cytokine secretion than those of control groups. Wild PRV challenge experiment is performed using mice as a model animal, achieving a protection rate of up to 86.67 %, which is much higher than those observed from the commercial Alum. This work not only demonstrates the high potentiality of TPMnXC in practical applications but also provides a new way to develop the Mn 2+ -loaded nanoadjuvant for veterinary vaccines.
研究领域:
兽医学
·
免疫学
·
纳米技术
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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