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

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dc.contributor.author Gillet, Nicolas A.
dc.contributor.author Cook, Lucy
dc.contributor.author Laydon, Daniel J.
dc.contributor.author Hlela, Carol
dc.contributor.author Verdonck, Kristien
dc.contributor.author Alvarez, Carolina
dc.contributor.author Gotuzzo Herencia, José Eduardo
dc.contributor.author Clark, Daniel
dc.contributor.author Farré, Lourdes
dc.contributor.author Bittencourt, Achiléa
dc.contributor.author Asquith, Becca
dc.contributor.author Taylor, Graham P.
dc.contributor.author Bangham, Charles R.M.
dc.date.accessioned 2022-01-04T20:31:50Z
dc.date.available 2022-01-04T20:31:50Z
dc.date.issued 2013
dc.identifier.uri https://hdl.handle.net/20.500.12866/10709
dc.description.abstract 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. en_US
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartofseries PLoS Pathogens
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Animals en_US
dc.subject Humans en_US
dc.subject major clinical study en_US
dc.subject Middle Aged en_US
dc.subject Adult en_US
dc.subject controlled study en_US
dc.subject polymerase chain reaction en_US
dc.subject Human T-lymphotropic virus 1 en_US
dc.subject Strongyloides en_US
dc.subject Strongyloides stercoralis en_US
dc.subject strongyloidiasis en_US
dc.subject Risk Factors en_US
dc.subject follow up en_US
dc.subject Coinfection en_US
dc.subject cell proliferation en_US
dc.subject dermatitis en_US
dc.subject HTLV-I Infections en_US
dc.subject Human T cell leukemia virus 1 en_US
dc.subject peripheral blood mononuclear cell en_US
dc.subject clonal variation en_US
dc.subject in vivo study en_US
dc.subject skin defect en_US
dc.subject Strongyloidiasis en_US
dc.subject T-Lymphocytes en_US
dc.subject virus load en_US
dc.subject cerebrospinal fluid en_US
dc.subject Vermes en_US
dc.subject Dermatitis en_US
dc.subject epigenetics en_US
dc.subject genetic similarity en_US
dc.subject Leukemia-Lymphoma, Adult T-Cell en_US
dc.subject Proviruses en_US
dc.subject Viral Load en_US
dc.title Strongyloidiasis and Infective Dermatitis Alter Human T Lymphotropic Virus-1 Clonality in vivo en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1371/journal.ppat.1003263
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.09
dc.relation.issn 1553-7374

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