PDF(Pubmed)
Abstract：
Pseudorabies virus (PRV) is the causative agent of Aujeszky\'s disease, which is responsible for enormous economic losses to the global pig industry. Although vaccination has been used to prevent PRV infection, the effectiveness of vaccines has been greatly diminished with the emergence of PRV variants. Therefore, there is an urgent need to develop anti-PRV drugs. Polyethylenimine (PEI) is a cationic polymer and has a wide range of antibacterial and antiviral activities. This study found that a low dose of 1 µg/mL of the 25-kDa linear PEI had significantly specific anti-PRV activity, which became more intense with increasing concentrations. Mechanistic studies revealed that the viral adsorption stage was the major target of PEI without affecting viral entry, replication stages, and direct inactivation effects. Subsequently, we found that cationic polymers PEI and Polybrene interfered with the interaction between viral proteins and cell surface receptors through electrostatic interaction to exert the antiviral function. In conclusion, cationic polymers such as PEI can be a category of options for defense against PRV. Understanding the anti-PRV mechanism also deepens host-virus interactions and reveals new drug targets for anti-PRV.IMPORTANCEPolyethylenimine (PEI) is a cationic polymer that plays an essential role in the host immune response against microbial infections. However, the specific mechanisms of PEI in interfering with pseudorabies virus (PRV) infection remain unclear. Here, we found that 25-kDa linear PEI exerted mechanisms of antiviral activity and the target of its antiviral activity was mainly in the viral adsorption stage. Correspondingly, the study demonstrated that PEI interfered with the virus adsorption stage by electrostatic adsorption. In addition, we found that cationic polymers are a promising novel agent for controlling PRV, and its antiviral mechanism may provide a strategy for the development of antiviral drugs.
摘要：
伪狂犬病病毒（PRV）是Aujeszky病的病原体，这对全球养猪业造成了巨大的经济损失。虽然疫苗已被用于预防PRV感染，随着PRV变种的出现,疫苗的有效性已经大大降低.因此,迫切需要开发抗PRV药物。聚乙烯亚胺（PEI）是一种阳离子聚合物，具有广泛的抗菌和抗病毒活性。这项研究发现，低剂量1µg/mL的25kDa线性PEI具有显着的特异性抗PRV活性，随着浓度的增加变得更加强烈。机制研究表明，病毒吸附阶段是PEI的主要目标，而不影响病毒进入，复制阶段，和直接失活效应。随后，我们发现阳离子聚合物PEI和Polybrene通过静电相互作用干扰病毒蛋白与细胞表面受体之间的相互作用，从而发挥抗病毒功能。总之,阳离子聚合物如PEI可以是防御PRV的一类选择。了解抗PRV机制还可以加深宿主病毒相互作用，并揭示抗PRV的新药物靶标。IMPORTANCE聚乙烯亚胺（PEI）是一种阳离子聚合物，在宿主针对微生物感染的免疫反应中起着至关重要的作用。然而,PEI干扰伪狂犬病病毒(PRV)感染的具体机制尚不清楚.这里,我们发现25kDa线性PEI发挥抗病毒活性的机制，其抗病毒活性的目标主要是在病毒吸附阶段。相应地,研究表明，PEI通过静电吸附干扰了病毒吸附阶段。此外,我们发现阳离子聚合物是一种有前途的控制PRV的新型试剂，其抗病毒机制可能为抗病毒药物的开发提供策略。
