Messingham Kelly N, Richards Paige T, Fleck Anthony, Patel Radhika A, Djurkovic Marija, Elliff Jonah, Connell Samuel, Crowe Tyler P, Munoz Gonzalez Juan, Gourronc Francoise, Dillard Jacob A, Davey Robert A, Klingelhutz Aloysius, Shtanko Olena, Maury Wendy
Department of Dermatology, University of Iowa, Iowa City, IA 52242, USA.
Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
Sci Adv. 2025 Jan 3;11(1):eadr6140. doi: 10.1126/sciadv.adr6140. Epub 2025 Jan 1.
Ebola virus (EBOV) causes severe human disease. During late infection, EBOV virions are on the skin's surface; however, the permissive skin cell types and the route of virus translocation to the epidermal surface are unknown. We describe a human skin explant model and demonstrate that EBOV infection of human skin via basal media increases in a time-dependent and dose-dependent manner. In the dermis, cells of myeloid, endothelial, and fibroblast origin were EBOV antigen-positive whereas keratinocytes harbored virus in the epidermis. Infectious virus was detected on the apical epidermal surface within 3 days, indicating that virus propagates and traffics through the explants. Purified human fibroblasts and keratinocytes supported EBOV infection ex vivo and both cell types required the phosphatidylserine receptor, AXL, and the endosomal protein, NPC1, for virus entry. This platform identified susceptible cell types and demonstrated dynamic trafficking of EBOV virions. These findings may explain person-to-person transmission via skin contact.
埃博拉病毒（EBOV）可引发严重的人类疾病。在感染后期，EBOV病毒粒子存在于皮肤表面；然而，允许病毒感染的皮肤细胞类型以及病毒转移至表皮表面的途径尚不清楚。我们描述了一种人类皮肤外植体模型，并证明通过基础培养基对人类皮肤进行EBOV感染呈时间依赖性和剂量依赖性增加。在真皮层，髓样、内皮和成纤维细胞来源的细胞呈EBOV抗原阳性，而角质形成细胞在表皮层中携带病毒。在3天内可在表皮顶端表面检测到感染性病毒，这表明病毒在整个外植体中进行繁殖和运输。纯化的人类成纤维细胞和角质形成细胞在体外支持EBOV感染，并且两种细胞类型都需要磷脂酰丝氨酸受体AXL和内体蛋白NPC1才能使病毒进入。该平台确定了易感细胞类型，并证明了EBOV病毒粒子的动态运输。这些发现可能解释了通过皮肤接触的人际传播。
