title: Strongyloidiasis and infective dermatitis alter human T lymphotropic virus-1 clonality in vivo.
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.
authors.affiliation: Section of Immunology, Wright-Fleming Institute, Imperial College London, London, United Kingdom. n.gillet@ulg.ac.be
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Gillet
authors.forename: Lucy
authors.initials: L
authors.lastname: Cook
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Laydon
authors.forename: Carol
authors.initials: C
authors.lastname: Hlela
authors.forename: Kristien
authors.initials: K
authors.lastname: Verdonck
authors.forename: Carolina
authors.initials: C
authors.lastname: Alvarez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gotuzzo
authors.forename: Daniel
authors.initials: D
authors.lastname: Clark
authors.forename: Lourdes
authors.initials: L
authors.lastname: Farré
authors.forename: Achiléa
authors.initials: A
authors.lastname: Bittencourt
authors.forename: Becca
authors.initials: B
authors.lastname: Asquith
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
mesh_terms: D000328:Adult; D000818:Animals; D060085:Coinfection; D003872:Dermatitis / Q000150:complications*; D015490:HTLV-I Infections / Q000150:complications* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000821:virology; D008875:Middle Aged; D011533:Proviruses / Q000502:physiology; D012307:Risk Factors; D017171:Strongyloides stercoralis; D013322:Strongyloidiasis / Q000150:complications* / Q000469:parasitology; D013601:T-Lymphocytes / Q000821:virology*; D019562:Viral Load