The HTLV-1c genomic landscape reveals host-virus interactions in a humanised mouse model of infection
Retroviruses infect a range of vertebrate hosts. Upon infection, the integrated provirus and host genome become enmeshed and have an ongoing reciprocal influence on one another, impacting both host and viral fitness. The integrated provirus thus has the potential to archive host-virus interactions.  Human T-cell leukemia virus 1 (HTLV-1) integrates its 9 kb genome into the human genome. HTLV-1 is endemic in Central Australia, with a prevalence of ~ 40% reported in some remote First Nations Communities. HTLV-1c is the divergent molecular variant of HTLV-1 found in Australia. HTLV-1 integration into the human genome has profound consequences on its target cell. However, the consequence of integration on HTLV-1 fitness is less well understood. To study the genetic impacts of HTLV-1 integration we have utilised the Oxford Nanopore Technologies (ONT) platform to generate contiguous, nucleotide-resolution HTLV-1c and HTLV-1a proviral genomes from infected humanised NSG mice. We identified HTLV-1c–human chimeric proviral genomes, which could encode novel protein products, render the proviral genome defective, and impact both host and viral gene expression.