Zhang Tianran, Yin Kangping, Xu Ying, Chen Kai, Huang Jinshan, Hao Bifang
Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, 212100, China.
Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, Sericultural Scientific Research Center, Chinese Academy of Agricultural Sciences, Zhenjiang, 212100, China.
Curr Microbiol. 2025 Jun 20;82(8):343. doi: 10.1007/s00284-025-04314-x.
Baculoviruses, such as Bombyx mori nucleopolyhedrovirus (BmNPV), are arthropod-specific DNA viruses with a complex entry mechanism that relies on host importin proteins for nuclear import. Despite significant advances in understanding viral entry, the precise role of importins in BmNPV nuclear import remains poorly understood. In this study, we identify importin α3 (IMPα3) as a critical mediator for the nuclear entry of the BmNPV nucleocapsid. Using RT-qPCR, we found that IMPα3, along with IMPα5 and IMP13, is upregulated during the early stages of BmNPV infection. Knockdown of IMPα3 significantly reduced viral infection rates, while overexpression of IMPα3 increased the infection rate by 24%. Functional domain analysis revealed that the N- and C-terminal regions of IMPα3 are essential for nucleocapsid nuclear entry, with truncation of either domain impairing this process. Interestingly, our findings indicate that BmNPV nuclear entry is independent of the classical RanGTP hydrolysis pathway, suggesting a Ran-independent mechanism for nucleocapsid transport. Further analysis confirmed that IMPα3, but not IMPβ, is essential for nuclear import, bypassing the need for traditional importin β-mediated transport. These results provide new insights into the role of IMPα3 in BmNPV infection and suggest that targeting IMPα3 could be a promising strategy for antiviral intervention.
杆状病毒，如家蚕核型多角体病毒（BmNPV），是节肢动物特异性DNA病毒，其进入机制复杂，依赖宿主输入蛋白进行核输入。尽管在理解病毒进入方面取得了重大进展，但输入蛋白在BmNPV核输入中的精确作用仍知之甚少。在本研究中，我们确定输入蛋白α3（IMPα3）是BmNPV核衣壳核进入的关键介质。使用RT-qPCR，我们发现IMPα3与IMPα5和IMP13一起在BmNPV感染的早期阶段上调。敲低IMPα3显著降低病毒感染率，而IMPα3的过表达使感染率提高了24%。功能域分析表明，IMPα3的N端和C端区域对于核衣壳核进入至关重要，任一结构域的截断都会损害这一过程。有趣的是，我们的研究结果表明，BmNPV核进入独立于经典的RanGTP水解途径，这表明存在一种不依赖Ran的核衣壳运输机制。进一步分析证实，IMPα3而非IMPβ对于核输入至关重要，从而绕过了传统输入蛋白β介导的运输需求。这些结果为IMPα3在BmNPV感染中的作用提供了新的见解，并表明靶向IMPα3可能是一种有前景的抗病毒干预策略。
