Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients

Retrovirology. 2016 Jan 8:13:3. doi: 10.1186/s12977-015-0236-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / blood
  • Antiviral Agents / therapeutic use
  • DNA, Viral / analysis
  • HTLV-I Infections / pathology*
  • HTLV-I Infections / virology*
  • Human T-lymphotropic virus 1 / immunology
  • Human T-lymphotropic virus 1 / isolation & purification*
  • Humans
  • Polymerase Chain Reaction
  • Proviruses / isolation & purification*
  • Time Factors
  • Transplant Recipients*
  • Transplantation / adverse effects*
  • Viral Load*

Substances

  • Antibodies, Viral
  • Antiviral Agents
  • DNA, Viral