Departamento de Anatomía Patológica, Instituto Nacional de Perinatología, Ciudad de Mexico, México.
Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de Mexico, México.
Clin Infect Dis. 2019 Mar 5;68(6):903-912. doi: 10.1093/cid/ciy616.
During pregnancy, the Zika virus (ZIKV) replicates in the placenta and central nervous system (CNS) of infected fetuses; nevertheless, the ability of ZIKV to replicate in other fetal tissues has not been extensively characterized.
We researched whether dissemination of congenitally-acquired ZIKV outside the CNS exists by searching for the accumulation of the viral envelope protein, ZIKV ribonucleic acid (RNA), and infectious viral particles in different organs of a deceased newborn with Congenital Zika Syndrome. A real-time qualitative polymerase chain reaction (qPCR) was used to detect ZIKV RNA in the brain, thymus, lungs, kidneys, adrenal glands, spleen, liver, and small intestine. The same tissues were analyzed by indirect immunofluorescence and immunoperoxidase assays using the monoclonal antibody 4G2 to detect ZIKV envelope antigens. Isolation of infectious ZIKV in a cell culture was carried out using brain and kidney samples.
A postmortem, virological analysis of multiple organs, such as the kidneys (epithelial cells in the renal tubules), lungs (bronchial epithelia), thymus (epithelial cells inside the Hassall's corpuscles), and brain (neurons, ependymal cells, and macrophages) revealed the presence of ZIKV RNA and envelope antigens. Other tissues of the deceased newborn tested positive by qPCR for Epstein-Barr virus and human herpesvirus 6, including the brain cortex (Epstein-Barr) and the thymus, kidneys, and adrenal glands (human herpesvirus 6). The kidneys were identified as a significant niche for viral replication, given that infectious particles were successfully isolated from renal tissues.
Our findings demonstrate the ability of congenitally-acquired ZIKV to produce disseminated infections and the viral tropism towards epithelial cells.
寨卡病毒（ZIKV）在感染胎儿的胎盘和中枢神经系统（CNS）中复制；然而，ZIKV 在其他胎儿组织中复制的能力尚未得到广泛描述。
我们通过搜索先天感染的 ZIKV 在 CNS 以外的传播情况，来研究这一问题，即在一名患有先天性寨卡综合征的已故新生儿的不同器官中寻找病毒包膜蛋白、ZIKV 核糖核酸（RNA）和感染性病毒颗粒的积累情况。使用实时定性聚合酶链反应（qPCR）检测大脑、胸腺、肺、肾、肾上腺、脾、肝和小肠中的 ZIKV RNA。使用单克隆抗体 4G2 通过间接免疫荧光和免疫过氧化物酶测定分析相同的组织，以检测 ZIKV 包膜抗原。使用脑和肾样本在细胞培养中分离传染性 ZIKV。
对多个器官（如肾脏（肾小管上皮细胞）、肺（支气管上皮细胞）、胸腺（哈索尔氏小体中的上皮细胞）和大脑（神经元、室管膜细胞和巨噬细胞））进行死后病毒学分析，发现存在 ZIKV RNA 和包膜抗原。通过 qPCR 对已故新生儿的其他组织进行检测，发现了 Epstein-Barr 病毒和人类疱疹病毒 6 的存在，包括大脑皮层（Epstein-Barr）和胸腺、肾脏和肾上腺（人类疱疹病毒 6）。肾脏被鉴定为病毒复制的重要部位，因为从肾组织中成功分离出了感染性颗粒。
我们的研究结果表明，先天感染的 ZIKV 具有产生播散性感染的能力，以及对上皮细胞的病毒嗜性。
