Rossignol Evan D, Peters Kristen N, Connor John H, Bullitt Esther
Department of Physiology & Biophysics, Boston University School of Medicine, Boston, MA, USA.
Department of Microbiology and National Emerging Infectious Disease Laboratory, Boston University School of Medicine, Boston, MA, USA.
Cell Microbiol. 2017 Aug;19(8). doi: 10.1111/cmi.12740. Epub 2017 Apr 18.
Zika virus (ZIKV) has been associated with morbidities such as Guillain-Barré, infant microcephaly, and ocular disease. The spread of this positive-sense, single-stranded RNA virus and its growing public health threat underscore gaps in our understanding of basic ZIKV virology. To advance knowledge of the virus replication cycle within mammalian cells, we use serial section 3-dimensional electron tomography to demonstrate the widespread remodelling of intracellular membranes upon infection with ZIKV. We report extensive structural rearrangements of the endoplasmic reticulum and reveal stages of the ZIKV viral replication cycle. Structures associated with RNA genome replication and virus assembly are observed integrated within the endoplasmic reticulum, and we show viruses in transit through the Golgi apparatus for viral maturation, and subsequent cellular egress. This study characterises in detail the 3-dimensional ultrastructural organisation of the ZIKV replication cycle stages. Our results show close adherence of the ZIKV replication cycle to the existing flavivirus replication paradigm.
寨卡病毒(ZIKV)与诸如格林-巴利综合征、婴儿小头畸形和眼部疾病等发病情况有关。这种正义单链RNA病毒的传播及其日益严重的公共卫生威胁凸显了我们在寨卡病毒基础病毒学认识上的差距。为了增进对该病毒在哺乳动物细胞内复制周期的了解,我们使用连续切片三维电子断层扫描技术来证明寨卡病毒感染后细胞内膜的广泛重塑。我们报告了内质网的广泛结构重排,并揭示了寨卡病毒复制周期的各个阶段。观察到与RNA基因组复制和病毒组装相关的结构整合在内质网中,并且我们展示了病毒在通过高尔基体进行病毒成熟及随后的细胞释放过程中的转运情况。本研究详细描述了寨卡病毒复制周期各阶段的三维超微结构组织。我们的结果表明寨卡病毒复制周期与现有的黄病毒复制模式紧密相符。