Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Department of Biology, New Iberia Research Center, University of Louisiana at Lafayette, Lafayette, Louisiana, United States of America.
PLoS Pathog. 2021 Nov 18;17(11):e1009855. doi: 10.1371/journal.ppat.1009855. eCollection 2021 Nov.
Vertical transmission of human immunodeficiency virus (HIV) can occur in utero, during delivery, and through breastfeeding. We utilized Positron Emission Tomography (PET) imaging coupled with fluorescent microscopy of 64Cu-labeled photoactivatable-GFP-HIV (PA-GFP-BaL) to determine how HIV virions distribute and localize in neonatal rhesus macaques two and four hours after oral viral challenge. Our results show that by four hours after oral viral exposure, HIV virions localize to and penetrate the rectal mucosa. We also used a dual viral challenge with a non-replicative viral vector and a replication competent SHIV-1157ipd3N4 to examine viral transduction and dissemination at 96 hours. Our data show that while SHIV-1157ipd3N4 infection can be found in the oral cavity and upper gastrointestinal (GI) tract, the small and large intestine contained the largest number of infected cells. Moreover, we found that T cells were the biggest population of infected immune cells. Thus, thanks to these novel technologies, we are able to visualize and delineate of viral distribution and infection throughout the entire neonatal GI tract during acute viral infection.
人类免疫缺陷病毒(HIV)可通过垂直传播在宫内、分娩时和通过母乳喂养传播。我们利用正电子发射断层扫描(PET)成像结合 64Cu 标记的光激活 GFP-HIV(PA-GFP-BaL)的荧光显微镜,来确定在口服病毒攻击后两小时和四小时,HIV 病毒颗粒如何在新生恒河猴的肠道中分布和定位。我们的结果表明,在口服病毒暴露后四个小时,HIV 病毒颗粒定位于并穿透直肠黏膜。我们还使用了具有复制能力的 SHIV-1157ipd3N4 的非复制性病毒载体的双重病毒攻击,以在 96 小时时检查病毒转导和传播。我们的数据表明,虽然 SHIV-1157ipd3N4 感染可以在口腔和上胃肠道(GI)中找到,但小肠和大肠包含了数量最多的感染细胞。此外,我们发现 T 细胞是受感染免疫细胞的最大群体。因此,借助这些新技术,我们能够在急性病毒感染期间可视化和描绘整个新生儿胃肠道中的病毒分布和感染情况。