Human retroviral latency: regulation and dynamics at the single-cell level

The human leukaemia virus HTLV-1, which is related to HIV, causes an aggressive leukaemia in 5 per cent of the people it infects, but how it does this is not understood. Like HIV, HTLV-1 integrates into the DNA of the infected cell, where it can lie dormant and avoid elimination by the immune response. Evidence from our studies of patients’ lymphocytes and the immune response and data from our molecular biological studies of HTLV-1-infected cells in the laboratory, show that the virus is carefully regulating its activity by causing intermittent bursts of expression of its genes, after which it returns to its dormant state.

We have assembled a set of techniques to identify the causes and quantify the kinetics of this gene bursting at the single-cell level. The results will answer fundamental questions on the persistence and pathogenesis of HTLV-1 and contribute to the growing understanding of mammalian gene bursting. We recently discovered that HTLV-1 can cause abnormal folding of DNA when integrated into host DNA. We aim to test the hypothesis that this abnormal folding in turn causes abnormal gene activity in the cell, which might be a significant cause of leukaemia.

The results of this study will help further our understanding of the mechanisms behind gene bursting and could help identify the cause of leukaemia.