Strongyloidiasis and Infective Dermatitis Alter Human T Lymphotropic Virus-1 Clonality in vivo

PLoS Pathogens

Graham P. Taylor¹  Eduardo Gotuzzo²  Achiléa Bittencourt³  Lourdes Farré³  Carolina Alvarez³  Daniel Clark³  Becca Asquith⁴  Lucy Cook⁵  Nicolas A. Gillet⁶  Carol Hlela⁶  Charles R. M. Bangham⁶  Daniel J. Laydon⁶  Kristien Verdonck⁶ 

[1] Complexo Hospitalar Universitário Prof. Edgard Santos, Department of Pathology, Federal University of Bahia, Salvador, Bahia, Brazil;Institute of Tropical Medicine, Antwerp, Belgium;Instituto de Medicina Tropical Alexander von Humboldt and Hospital Nacional Cayetano Heredia, Universidad Peruana Cayetano Heredia, Lima, Peru;Laboratory of Experimental Pathology, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil;Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) of University of Liège (ULg), Liège, Belgium;Section of Immunology, Wright-Fleming Institute, Imperial College London, London, United Kingdom

关键词: Cloning;    HTLV-1;    Strongyloides;    Blood;    T cells;    Co-infections;    Skin infections;    Lesions;   

DOI  :  10.1371/journal.ppat.1003263

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Human T-lymphotropic Virus-1 (HTLV-1) is a retrovirus that persists lifelong by driving clonal proliferation of infected T-cells. HTLV-1 causes a neuroinflammatory disease and adult T-cell leukemia/lymphoma. Strongyloidiasis, a gastrointestinal infection by the helminth Strongyloides stercoralis, and Infective Dermatitis associated with HTLV-1 (IDH), appear to be risk factors for the development of HTLV-1 related diseases. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the HTLV-1-infected T-cell population (i.e. the number of distinct clones and abundance of each clone). A newly developed biodiversity estimator called “DivE” was used to estimate the total number of clones in the blood. We found that the major determinant of proviral load in all subjects without leukemia/lymphoma was the total number of HTLV-1-infected clones. Nevertheless, the significantly higher proviral load in patients with strongyloidiasis or IDH was due to an increase in the mean clone abundance, not to an increase in the number of infected clones. These patients appear to be less capable of restricting clone abundance than those with HTLV-1 alone. In patients co-infected with Strongyloides there was an increased degree of oligoclonal expansion and a higher rate of turnover (i.e. appearance and disappearance) of HTLV-1-infected clones. In Strongyloides co-infected patients and those with IDH, proliferation of the most abundant HTLV-1+ T-cell clones is independent of the genomic environment of the provirus, in sharp contrast to patients with HTLV-1 infection alone. This implies that new selection forces are driving oligoclonal proliferation in Strongyloides co-infection and IDH. We conclude that strongyloidiasis and IDH increase the risk of development of HTLV-1-associated diseases by increasing the rate of infection of new clones and the abundance of existing HTLV-1+ clones.

【 授权许可】

CC BY