Zhou Linda, Leung Thomas H
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
JID Innov. 2025 Jan 11;5(3):100348. doi: 10.1016/j.xjidi.2025.100348. eCollection 2025 May.
Viruses are well-documented agents of specific skin diseases. However, their role and precise mechanism of action in other skin diseases remain unknown. We describe a single-cell RNA-sequencing-based strategy to interrogate human skin biopsies for viral transcripts, permitting detection of viral infection within a sample, single-cell resolution of virally infected cells and identification of subsequent transcriptomic perturbations. We validate our pipeline with 100% sensitivity and specificity by (i) detecting Merkel cell polyomavirus in Merkel cell carcinoma samples, (ii) detecting specific human papillomavirus strains in known human papillomavirus-positive tumors, and (iii) detecting rubella virus transcripts in patients with known rubella-associated granulomas. We identify infection of known and previously unreported cell types and elucidate viral-mediated transcriptional perturbations. In rubella virus-infected cells, we discover macrophage-specific evolution of the rubella virus E1 capsid protein. Finally, we interrogate skin biopsies from many established nonvirally mediated inflammatory skin diseases and do not find consistent evidence of viral infection in any condition. Combining single-cell RNA-sequencing data with virome detection strategies represents a potentially powerful approach to investigate and elucidate virus-mediated gene regulation in health and disease.
病毒是特定皮肤病的有充分文献记载的病原体。然而，它们在其他皮肤病中的作用和精确作用机制仍不清楚。我们描述了一种基于单细胞RNA测序的策略，用于检测人类皮肤活检组织中的病毒转录本，从而能够在样本中检测病毒感染、以单细胞分辨率鉴定病毒感染细胞，并识别随后的转录组扰动。我们通过以下方式验证了我们的流程，其灵敏度和特异性均为100%：（i）在默克尔细胞癌样本中检测默克尔细胞多瘤病毒；（ii）在已知的人乳头瘤病毒阳性肿瘤中检测特定的人乳头瘤病毒株；（iii）在已知风疹相关肉芽肿患者中检测风疹病毒转录本。我们识别出已知和先前未报告的细胞类型的感染，并阐明病毒介导的转录扰动。在风疹病毒感染的细胞中，我们发现了风疹病毒E1衣壳蛋白的巨噬细胞特异性进化。最后，我们对许多已确诊的非病毒介导的炎症性皮肤病的皮肤活检组织进行检测，未在任何情况下发现一致的病毒感染证据。将单细胞RNA测序数据与病毒组检测策略相结合，是一种研究和阐明健康与疾病中病毒介导的基因调控的潜在有力方法。
