Retroviruses infect a range of vertebrate hosts. Upon infection, the viral genome is reverse transcribed and integrated into the host genome. The integrated provirus and host genome are enmeshed and have an ongoing reciprocal influence on one another, impacting both host and viral fitness.
Human T-cell leukemia virus 1 (HTLV-1) is a pathogenic retrovirus, which upon infection integrates its 9kb genome into the human genome. ~10-20 million people carry HTLV-1 worldwide. Central Australia has the highest rate of HTLV-1 infection globally, with a prevalence of ~40% reported in some Communities. HTLV-1c is the highly divergent molecular variant of HTLV-1 found in Australia.
We have used the Oxford Nanopore Technologies long-read sequencing platform to perform the first in-depth, nucleotide resolution characterisation of the continuous HTLV-1 genome in a patient cohort, as well as integration site selection and genome structure in a mouse model of HTLV-1c associated disease. Our studies have revealed a highly defective proviral landscape and an archive of host-viral interactions with relevance to strategies used to target disease.
Natasha Jansz is a biomedical scientist with a background in developmental epigenetics and genomics. Natasha trained at WEHI, completing her PhD under the supervision of Professor Marnie Blewitt. She was awarded Human Frontiers and EMBO Postdoctoral Fellowships to train at the Helmholtz Institute of Epigenetics and Stem Cells in Munich, where she studied transposable element regulation in the preimplantation embryo. In 2021, Natasha has joined Professor Geoffrey Faulkner at Mater Research UQ, supported by an NHMRC Investigator Grant, to investigate the epigenetic mechanisms governing retrovirus regulation in infectious and malignant disease, with a focus on HTLV-1c.