title: HTLV-1 drives vigorous clonal expansion of infected CD8(+) T cells in natural infection.
abstract: BACKGROUND
  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 vivo, but the relative abundance and clonal composition of the two infected subpopulations have not been studied. We used a high-throughput DNA sequencing protocol to map and quantify HTLV-1 proviral integration sites in separated populations of CD4(+) cells, CD8(+) cells and unsorted peripheral blood mononuclear cells from 12 HTLV-1-infected individuals.
  
  
  RESULTS
  We show that the infected CD8(+) cells constitute a median of 5% of the HTLV-1 proviral load. However, HTLV-1-infected CD8(+) clones undergo much greater oligoclonal proliferation than the infected CD4(+) clones in infected individuals, regardless of disease manifestation. The CD8(+) clones are over-represented among the most abundant clones in the blood and are redetected even after several years.
  
  
  CONCLUSIONS
  We conclude that although they make up only 5% of the proviral load, the HTLV-1-infected CD8(+) T-cells make a major impact on the clonal composition of HTLV-1-infected cells in the blood. The greater degree of oligoclonal expansion observed in the infected CD8(+) T cells, contrasts with the CD4(+) phenotype of ATL; cases of CD8(+) adult T-cell leukaemia/lymphoma are rare. This work is consistent with growing evidence that oligoclonal expansion of HTLV-1-infected cells is not sufficient for malignant transformation.
authors.affiliation: Section of Virology, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, W2 1PG, UK. anat.melamed07@imperial.ac.uk.
authors.forename: Anat
authors.initials: A
authors.lastname: Melamed
authors.affiliation: Section of Virology, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, W2 1PG, UK. d.laydon@imperial.ac.uk.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Laydon
authors.affiliation: Section of Virology, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, W2 1PG, UK. halkhatib85@hotmail.com.
authors.forename: Hebah
authors.initials: H
authors.lastname: Al Khatib
authors.affiliation: Section of Virology, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, W2 1PG, UK. a.rowan@imperial.ac.uk.
authors.forename: Aileen G
authors.initials: AG
authors.lastname: Rowan
authors.affiliation: Section of Virology, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, W2 1PG, UK. g.p.taylor@imperial.ac.uk.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.affiliation: Section of Virology, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, W2 1PG, UK. c.bangham@imperial.ac.uk.
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology*; D002999:Clone Cells; D015490:HTLV-I Infections / Q000276:immunology* / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008875:Middle Aged; D011533:Proviruses; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology*; D019562:Viral Load; D016662:Virus Integration; D017735:Virus Latency