The Nature of HTLV-1 Provirus in Naturally Infected Individuals Analyzed by Viral DNA-Capture-Seq Approach

The retrovirus HTLV-1 integrates into the host cellular DNA, achieves persistent infection, and induces human diseases. Here we demonstrate that viral DNA-capture-seq is useful to characterize HTLV-1 provirus in naturally virus-infected individuals, providing comprehensive information about the proviral structure and the viral integration site. We analyzed peripheral blood from 98 naturally HTLV-1-infected individuals and found that defective proviruses were present not only in patients with leukemia, but also in those with other clinical entities. We further demonstrated that infected clones with defective-type exhibited higher degree of clonal abundance than those with full-length type. The frequency of defective-type in HTLV-1-infected humanized mice was lower than that in infected individuals, indicating that defective proviruses were rare at the initial phase of infection but preferentially selected during persistent infection. These results demonstrate robustness of viral DNA-capture-seq for HTLV-1 infection and shed light on its potential application for other virus-associated cancers in human.