Li Jian, Zhu Changyang, Meng Yang, Zhang Linliang, Liu Cong, Qin Yali, Chen Mingzhou
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
College of Life Sciences, Hubei University, Wuhan, China.
J Virol. 2025 Mar 18;99(3):e0198024. doi: 10.1128/jvi.01980-24. Epub 2025 Feb 20.
Zika virus (ZIKV) is associated with microcephaly in neonates and neurological disorders in adults. Chronic ZIKV infection has been identified in the testes, indicating that the virus can lead to prolonged illness, yet its pathogenesis remains poorly understood. Here, we found that ZIKV infection does not induce significant cell death in mouse macrophages despite the critical role that cell death plays in the antiviral immune response. Furthermore, we discovered that ZIKV infection impairs the activation of the NLPR3-dependent inflammasome and inhibits apoptosis. Consequently, we investigated the regulatory mechanism of the NLRP3 inflammasome and apoptosis in the context of ZIKV infection. Our results revealed significant reductions in the protein expression levels of NLRP3 and A20, attributable to post-transcriptional or translational effects during ZIKV infection. These findings suggest that ZIKV infection may disrupt cell death pathways, leading to its pathogenicity.IMPORTANCEZika virus (ZIKV), first isolated from a nonhuman primate in Africa in 1947, was relatively understudied until 2016. By then, ZIKV had already been reported in more than 20 countries and territories. The infection poses a significant risk, as it is associated with microcephaly in infants and neurological disorders in adults; however, the underlying mechanisms responsible for these severe outcomes remain unclear. In this study, we demonstrate that ZIKV infection significantly reduces the expression of NLRP3 and A20 proteins through post-transcriptional or translational processes, which leads to inhibited cell death. These findings are critical because cell death plays a vital role in the host's antiviral immune response. Our findings highlight how ZIKV infection compromises essential cell death pathways, raising serious concerns about its pathogenesis. A comprehensive understanding of this disruption is vital for developing targeted interventions to mitigate the virus' impact on public health.
寨卡病毒（ZIKV）与新生儿小头畸形以及成人神经疾病有关。已在睾丸中发现慢性寨卡病毒感染，这表明该病毒可导致病程迁延，但对其发病机制仍知之甚少。在此，我们发现，尽管细胞死亡在抗病毒免疫反应中起关键作用，但寨卡病毒感染并不会在小鼠巨噬细胞中诱导显著的细胞死亡。此外，我们发现寨卡病毒感染会损害NLRP3依赖性炎性小体的激活并抑制细胞凋亡。因此，我们研究了寨卡病毒感染情况下NLRP3炎性小体和细胞凋亡的调控机制。我们的结果显示，NLRP3和A20的蛋白表达水平显著降低，这归因于寨卡病毒感染期间的转录后或翻译效应。这些发现表明，寨卡病毒感染可能会破坏细胞死亡途径，从而导致其致病性。
重要性
寨卡病毒（ZIKV）于1947年首次从非洲的一只非人类灵长类动物中分离出来，直到2016年之前其研究相对较少。到那时，寨卡病毒已在20多个国家和地区被报道。这种感染带来了重大风险，因为它与婴儿小头畸形和成人神经疾病有关；然而，导致这些严重后果的潜在机制仍不清楚。在本研究中，我们证明寨卡病毒感染通过转录后或翻译过程显著降低NLRP3和A20蛋白的表达，从而导致细胞死亡受到抑制。这些发现至关重要，因为细胞死亡在宿主的抗病毒免疫反应中起着至关重要的作用。我们的发现突出了寨卡病毒感染如何损害基本的细胞死亡途径，引发了对其发病机制的严重关注。全面了解这种破坏对于开发有针对性的干预措施以减轻该病毒对公共卫生的影响至关重要。
