Multiple integrations of human T-lymphotropic virus type 1 proviruses in the engrafted cells from the asymptomatic carriers in NOD/SCID/gammacnull mice

Intervirology. 2010;53(4):229-39. doi: 10.1159/000302760. Epub 2010 Mar 30.

Abstract

Objectives: Successful engraftment of human T-lymphotropic virus type 1 (HTLV-1)-infected cells and a marked increase of proviral DNA loads (PVLs) in non-obese diabetic/severe combined immunodeficient (NOD/SCID)/gammac(null) (NOG) mice have been reported. Whether the increased PVL in transplanted mice is due to the new infection of HTLV-1 was examined.

Methods: Mononuclear cells from 3 NOG mice with primary engraftment from asymptomatic HTLV-1 carriers were transplanted into a second group of NOG mice. HTLV-1 PVL, proviral integration by fluorescence in situ hybridization assay, expression of viral antigen, and T-cell clonality were analyzed.

Results: The PVLs in the secondarily transplanted NOG mice were significantly higher than those of primarily transplanted NOG mice. Multiple signals of HTLV-1 proviruses in the nucleus of the infected cells were revealed by fluorescence in situ hybridization analysis. Expression of HTLV-1 tax/rex mRNA and antigen was observed. The variety of T-cell clones was limited in the transplanted NOG mice.

Conclusions: Multiple proviral integrations were considered to be due to the new infection from HTLV-1-infected cells to the other cells. Only a certain fraction of T cells seemed to have selectively survived in NOG mice after engraftment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier State / virology*
  • Cell Transplantation
  • Female
  • HTLV-I Infections / virology*
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / isolation & purification*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Proviruses / genetics
  • Proviruses / isolation & purification*
  • Transplantation, Heterologous
  • Transplantation, Homologous