title: Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients.
abstract: BACKGROUND
  Human T-lymphotropic virus type 1 (HTLV-1) infects an estimated 10 million persons globally with transmission resulting in lifelong infection. Disease, linked to high proviral load, occurs in a minority. In established infection HTLV-1 replicates through infectious spread and clonal expansion of infected lymphocytes. Little is known about acute HTLV-1 infection. The kinetics of early HTLV-1 infection, following transplantation-acquired infection in three recipients from one HTLV-1 infected donor, is reported. The recipients were treated with two HTLV-1 enzyme inhibitors 3 weeks post exposure following the detection of HTLV-1 provirus at low level in each recipient. HTLV-1 infection was serially monitored by serology, quantification of proviral load and HTLV-1 2LTR DNA circles and by HTLV-1 unique integration site analysis.
  
  
  RESULTS
  HTLV-1 antibodies were first detected 16-39 days post-transplantation. HTLV-1 provirus was detected by PCR on day 16-23 and increased by 2-3 log by day 38-45 with a peak proviral doubling time of 1.4 days, after which steady state was reached. The rapid proviral load expansion was associated with high frequency of HTLV-1 2LTR DNA circles. The number of HTLV-1 unique integration sites was high compared with established HTLV-1 infection. Clonal expansion of infected cells was detected as early as day 37 with high initial oligoclonality index, consistent with early mitotic proliferation.
  
  
  CONCLUSIONS
  In recipients infected through organ transplantation HTLV-1 disseminated rapidly despite early anti-HTLV-1 treatment. Proviral load set point was reached within 6 weeks. Seroconversion was not delayed. Unique integration site analysis and HTLV-1 2LTR DNA circles indicated early clonal expansion and high rate of infectious spread.
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK. l.cook@imperial.ac.uk.
authors.forename: Lucy B M
authors.initials: LB
authors.lastname: Cook
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, 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, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK. m.demontis@imperial.ac.uk.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Demontis
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK. d.laydon@imperial.ac.uk.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Laydon
authors.affiliation: Department of Biology and Hull York Medical School, Centre for Immunology and Infection, University of York, York, UK. james.fox@york.ac.uk.
authors.forename: James M
authors.initials: JM
authors.lastname: Fox
authors.affiliation: HIV and Antiviral Group, Public Health England, 61, Colindale Avenue, London, UK. Jennifer.Tosswill@phe.gov.uk.
authors.forename: Jennifer H C
authors.initials: JH
authors.lastname: Tosswill
authors.affiliation: Department of Renal Medicine, Manchester Royal Infirmary, Central Manchester NHS Foundation Trust, Oxford Road, Manchester, UK. declandefreitas@beaumont.ie.
authors.forename: Declan
authors.initials: D
authors.lastname: de Freitas
authors.affiliation: Department of Infection and Tropical Medicine, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK. David.Price@nuth.nhs.uk.
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Price
authors.affiliation: John Walls Renal Unit, Leicester General Hospital, Gwendolen Road, Leicester, UK. james.medcalf@nhs.net.
authors.forename: James F
authors.initials: JF
authors.lastname: Medcalf
authors.affiliation: Department of Biology and Hull York Medical School, Centre for Immunology and Infection, University of York, York, UK. Fabiola.Martin@hyms.ac.uk.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Martin
authors.affiliation: Organ Donation and Transplantation, NHS Blood and Transplant, Bristol, UK. james.neuberger@nhsbt.nhs.uk.
authors.forename: James M
authors.initials: JM
authors.lastname: Neuberger
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK. c.bangham@imperial.ac.uk.
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK. g.p.taylor@imperial.ac.uk.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000032:analysis; D015490:HTLV-I Infections / Q000473:pathology* / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000302:isolation & purification*; D013997:Time Factors; D066027:Transplant Recipients; D014180:Transplantation / Q000009:adverse effects*; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D004279:DNA, Viral