Department of Microbiology.
Graduate School of Biomedical Sciences, and.
JCI Insight. 2024 Jul 25;9(17):e172261. doi: 10.1172/jci.insight.172261.
In humans, lymph nodes are the primary site of measles virus (MeV) replication. To understand the immunological events that occur at this site, we infected human lymphoid tissue explants using a pathogenic strain of MeV that expresses GFP. We found that MeV infected 5%-15% of cells across donors. Using single-cell RNA-Seq and flow cytometry, we found that while most of the 29 cell populations identified in the lymphoid culture were susceptible to MeV, there was a broad preferential infection of B cells and reduced infection of T cells. Further subsetting of T cells revealed that this reduction may be driven by the decreased infection of naive T cells. Transcriptional changes in infected B cells were dominated by an interferon-stimulated gene (ISG) signature. To determine which of these ISGs were most substantial, we evaluated the proteome of MeV-infected Raji cells by mass spectrometry. We found that IFIT1, IFIT2, IFIT3, ISG15, CXCL10, MX2, and XAF1 proteins were the most highly induced and positively correlated with their expression in the transcriptome. These data provide insight into the immunological events that occur in lymph nodes during infection and may lead to the development of therapeutic interventions.
在人类中，淋巴结是麻疹病毒（MeV）复制的主要部位。为了了解在此部位发生的免疫事件，我们使用表达 GFP 的致病性 MeV 株感染人淋巴组织外植体。我们发现，MeV 感染了不同供体之间的 5%-15%的细胞。通过单细胞 RNA-Seq 和流式细胞术，我们发现，虽然淋巴培养物中鉴定的 29 种细胞群中的大多数都容易受到 MeV 的感染，但 B 细胞的感染广泛偏好，T 细胞的感染减少。进一步对 T 细胞进行亚群分析表明，这种减少可能是由于幼稚 T 细胞的感染减少所致。感染 B 细胞的转录变化主要由干扰素刺激基因（ISG）特征主导。为了确定哪些 ISGs 最为显著，我们通过质谱法评估了 MeV 感染的 Raji 细胞的蛋白质组。我们发现，IFIT1、IFIT2、IFIT3、ISG15、CXCL10、MX2 和 XAF1 蛋白的诱导水平最高，与转录组中的表达呈正相关。这些数据提供了在感染期间淋巴结中发生的免疫事件的深入了解，并可能导致治疗干预措施的发展。
