Abstract 3174: The host genomic environment of the provirus determines the abundance of BLV-infected clones

Abstract

Abstract Human T-lymphotropic Virus 1 (HTLV-1) induces a persistent infection that remains generally asymptomatic. Nevertheless, in a small proportion of individuals and after a long latency, HTLV-1 infection leads to leukemia or lymphoma. Onset of clinical manifestations correlates with a persistently elevated number of infected cells. Because the vast majority of cells are infected at early stages, primary infection is a crucial period for HTLV-1 persistence and pathogenesis. Since HTLV-1 is transmitted through breast feeding and because systematic population screenings are rare, there is a lack of available samples at early infection. Therefore, we addressed this question in a closely related animal model by inoculating cows with Bovine Leukemia Virus (BLV). Initial BLV provirus insertion is not random but occurs nearby transcribed genomic regions (genes and CpG islands). This pattern of integration is highly similar to the observed pattern in HTLV-1 in vitro experiments. Later on, the proportion of clone carrying a provirus in transcribed regions decreases to reach levels comparable to those observed in asymptomatic HTLV-1 carriers. The negative selection against BLV clones carrying a provirus nearby transcribed regions is more efficient in animals that will subsequently present low proviral load set point. Finally, like for HTLV-1 infected people, the abundance of the BLV infected clones correlates with the integration of the provirus in transcribed regions. These observations highlight the high similarities between BLV and HTLV-1 clonality and suggest a key role exerted by the host immune system during primary infection. Citation Format: Nicolas Gillet, Alix de Brogniez, Nathalie Renotte, Geronimo Gutierrez, Irene Alvarez, Karina Trono, Luc Willems. The host genomic environment of the provirus determines the abundance of BLV-infected clones. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3174. doi:10.1158/1538-7445.AM2014-3174