Hasson Jenna M, Katusiime Mary Grace, Capoferri Adam A, Bale Michael J, Luke Brian T, Shao Wei, Cotton Mark F, van Zyl Gert, Patro Sean C, Kearney Mary F
HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
bioRxiv. 2025 May 27:2025.05.23.655786. doi: 10.1101/2025.05.23.655786.
HIV-1 proviral landscapes were investigated using near full-length HIV single-genome sequencing on blood samples from 5 children with vertically acquired infection and on ART for ~7-9 years. Proviral structures were compared to published datasets in children prior to ART, children on short-term ART, and adults on ART. We found a strong selection for large internal proviral deletions in children, especially deletions of the gene. Only 2.5% of the proviruses were sequence-intact, lower than in the comparative datasets from adults. Of the proviruses that retained the gene, >80% contained two or more defects, most commonly stop codons and/or start mutations. Significantly fewer defects in the major splice donor site (MSD) and packaging signal were found in the children on short or long-term ART compared to the adults, and was more frequently defective in children. These results suggest that different selection pressures shape the proviral landscape in children compared to adults and reveal potentially different genetic regions to target for measuring the intact HIV reservoir and for achieving HIV remission in children.
利用近全长HIV单基因组测序技术，对5名垂直感染且接受抗逆转录病毒治疗（ART）约7 - 9年的儿童的血液样本进行了HIV-1前病毒格局研究。将前病毒结构与ART治疗前儿童、短期接受ART治疗的儿童以及接受ART治疗的成人的已发表数据集进行了比较。我们发现儿童体内存在对大型内部前病毒缺失的强烈选择，尤其是 基因的缺失。只有2.5%的前病毒序列完整，低于成人的比较数据集。在保留 基因的前病毒中，超过80%存在两个或更多缺陷，最常见的是终止密码子和/或起始突变。与成人相比，短期或长期接受ART治疗的儿童中，主要剪接供体位点（MSD）和包装信号中的缺陷明显较少，并且 在儿童中更频繁地出现缺陷。这些结果表明，与成人相比，不同的选择压力塑造了儿童的前病毒格局，并揭示了在测量儿童完整HIV储存库以及实现儿童HIV缓解方面可能需要靶向的不同基因区域。
