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.
Highlights
Human T-lymphotropic virus type 1 (HTLV-1) causes adult Tcell leukemia-lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
Strongyloidiasis, a gastrointestinal infection by an helminth (Strongyloides stercoralis) and Infective Dermatitis associated with HTLV-1 (IDH), a skin inflammation with bacterial infection, appear to increase the risk of developing HTLV-1-related diseases
We have shown that the significantly increased proviral load in HTLV-1-infected individuals with IDH or strongyloidiasis is due to an increase in the mean clone abundance, not to an increase in the number of infected clones
Summary
Human T-lymphotropic virus type 1 (HTLV-1) causes adult Tcell leukemia-lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been estimated that 10 to 20 million persons live with HTLV-1 infection worldwide. A small proportion (up to 7%, depending on the area) of HTLV-1-infected individuals develop disease, while the majority remain asymptomatic carriers (ACs). The HTLV-1 proviral load remains stable within each infected person and correlates with the outcome of infection. Infectious transmission of HTLV-1 across the virological synapse [5] is believed to be important early in infection, whereas mitotic replication is thought to be mainly responsible for maintaining proviral load once a persistent infection has been established and has reached equilibrium with the immune response [6]. HTLV-1 clonal expansion in vivo is enhanced by proviral integration in an actively transcribed area of the genome [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
