Webb Andrew L, Schindell Brayden G, Soule Geoff, Siddik Abu B, Abrenica Bernard, Memon Harram, Su Ruey-Chyi, Safronetz David, Kindrachuk Jason
Department of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.
Npj Viruses. 2024 Apr 11;2(1):12. doi: 10.1038/s44298-024-00022-8.
Ebola virus (EBOV) is able to persist and actively replicate in the reproductive tract of male disease survivors months or years after recovery from Ebola virus disease (EVD). Persistent EBOV infections are usually asymptomatic and can be transmitted sexually, but the host and viral factors that mediate these infections have not been characterized. We investigated the interaction between host and viral factors during EBOV infection of the blood testis barrier (BTB), with a focus on Sertoli cells as a potential reservoir for viral persistence. We assessed viral replication kinetics and host responses of mouse testicular Leydig cells and Sertoli cells infected with EBOV Makona (i.e. infectious EBOV) and collected samples up to 28 days post-infection. Viral replication was apparent in both cell lines, but intracellular early viral loads were much higher in Leydig cells compared to Sertoli cells. We used RNAseq analysis to characterize transcriptomic responses of Leydig cells and Sertoli cells to EBOV infection over time. Further investigation of early interactions between host cells and EBOV was performed using virus-like particles (EBOV trVLP) and assays of phosphorylation-based cell signaling. Our findings indicate that virus-treated Sertoli cells responded more rapidly and robustly than Leydig cells, and with a particular emphasis on detection of, and response to, external stimuli. We discuss how the roles played by Sertoli cells in immune privilege and spermatogenesis may affect their initial and continued response to EBOV infection in a manner that could facilitate asymptomatic persistence.
埃博拉病毒（EBOV）能够在男性埃博拉病毒病（EVD）康复后的数月或数年内在其生殖道中持续存在并活跃复制。持续性埃博拉病毒感染通常无症状，可通过性传播，但介导这些感染的宿主和病毒因素尚未明确。我们研究了在埃博拉病毒感染血睾屏障（BTB）过程中宿主与病毒因素之间的相互作用，重点关注支持细胞作为病毒持续存在的潜在储存库。我们评估了感染埃博拉病毒马科纳株（即具有传染性的埃博拉病毒）的小鼠睾丸间质细胞和支持细胞的病毒复制动力学及宿主反应，并在感染后28天内收集样本。两种细胞系中均可见病毒复制，但与支持细胞相比，间质细胞内早期病毒载量要高得多。我们使用RNA测序分析来表征间质细胞和支持细胞随时间对埃博拉病毒感染的转录组反应。使用病毒样颗粒（埃博拉病毒三聚体病毒样颗粒）和基于磷酸化的细胞信号转导分析对宿主细胞与埃博拉病毒之间的早期相互作用进行了进一步研究。我们的研究结果表明，病毒处理后的支持细胞比间质细胞反应更快、更强烈，尤其侧重于对外部刺激的检测和反应。我们讨论了支持细胞在免疫豁免和精子发生中所起的作用可能如何以一种促进无症状持续存在的方式影响其对埃博拉病毒感染的初始和持续反应。
