Abstract 2715: Host genomic environment determines HTLV-1 clone size in vivo

HTLV-1 persists by driving clonal proliferation of infected T-lymphocytes. A high proviral load predisposes to the inflammatory and malignant diseases associated with HTLV-1. Yet the reasons for the remarkable variation within and between individuals in the size of HTLV-1-infected clones remain unknown. We devised a high-throughput protocol to map the genomic location and quantify the abundance of >91,000 distinct integration sites from 61 HTLV-1+ individuals and >2,100 sites from in vitro infection. We show that a typical HTLV-1-infected host carries between 500 and 5000 distinct integrated proviral clones. We demonstrate that negative selection dominates during chronic infection, favouring survival of proviruses integrated in transcriptionally silenced DNA: this selection is significantly stronger in asymptomatic carriers. The high proviral load characteristic of HTLV-1-associated inflammatory disease results from a larger number of integrated proviruses and not as previously believed from a difference in clonality. The abundance of surviving integrated proviruses is determined by genomic features of the flanking DNA and the transcriptional orientation of the provirus relative to the nearest host gene. HTLV-1 clonal expansion in vivo is favoured by orientation of the provirus in the same sense as the nearest host gene. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2715. doi:10.1158/1538-7445.AM2011-2715