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Human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) both cause lifelong persistent infections, but differ in their clinical outcomes. HTLV-1 infection causes a chronic or acute T-lymphocytic malignancy in up to 5% of infected individuals whereas HTLV-2 has not been unequivocally linked to a T-cell malignancy. Virus-driven clonal proliferation of(More)
MOTIVATION The relative abundance of retroviral insertions in a host genome is important in understanding the persistence and pathogenesis of both natural retroviral infections and retroviral gene therapy vectors. It could be estimated from a sample of cells if only the host genomic sites of retroviral insertions could be directly counted. When host genomic(More)
The regulation of proviral latency is a central problem in retrovirology. We postulate that the genomic integration site of human T lymphotropic virus type 1 (HTLV-1) determines the pattern of expression of the provirus, which in turn determines the abundance and pathogenic potential of infected T cell clones in vivo. We recently developed a high-throughput(More)
Estimation of immunological and microbiological diversity is vital to our understanding of infection and the immune response. For instance, what is the diversity of the T cell repertoire? These questions are partially addressed by high-throughput sequencing techniques that enable identification of immunological and microbiological "species" in a sample.(More)
Human T lymphotropic virus type 1 (HTLV-1) causes a range of chronic inflammatory diseases and an aggressive malignancy of T lymphocytes known as adult T-cell leukaemia/lymphoma (ATLL). A cardinal feature of HTLV-1 infection is the presence of expanded clones of HTLV-1-infected T cells, which may persist for decades. A high viral burden (proviral load) is(More)
HTLV-1 causes proliferation of clonal populations of infected T cells in vivo, each clone defined by a unique proviral integration site in the host genome. The proviral load is strongly correlated with odds of the inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is evidence that asymptomatic HTLV-1 carriers(More)
Human T-lymphotropic virus type 1 (HTLV-1) infects an estimated 10 million persons globally with transmission resulting in lifelong infection. Disease, linked to high proviral load, occurs in a minority. In established infection HTLV-1 replicates through infectious spread and clonal expansion of infected lymphocytes. Little is known about acute HTLV-1(More)
Human T-lymphotropic Virus Type I (HTLV-1) is a retrovirus that persistently infects 5–10 million individuals worldwide and causes disabling or fatal inflammatory and malignant diseases. The majority of the HTLV-1 proviral load is found in CD4+ T cells, and the phenotype of adult T cell leukemia (ATL) is typically CD4+. HTLV-1 also infects CD8+ cells in(More)
Adult T cell Leukaemia Lymphoma [ATL], a mature T-cell neoplasm has been classified into 4 subtypes: smouldering; chronic leukaemia; lymphoma and acute leukaemia. The diagnosis depends on clinical features, the immunophenotype, and demonstration of HTLV-1 infection & ideally of monoclonal proviral integration. The typical immunophenotype of ATL is not(More)
HTLV-1 selectively infects CD4+ T cells in vivo, with a minor population carried in CD8+ T cells. We previously established a method for the analysis of the clonality (clone frequency distribution) of infected cells by mapping and quantifying HTLV-1 proviral integration sites using high-throughput sequencing (Gillet et al, Blood, 2011; Cook et al, Blood,(More)