Assessment of HTLV-1 proviral load, LAT, BIM, c-FOS and RAD51 gene expression in adult T cell leukemia/lymphoma

Med Microbiol Immunol. 2017 Aug;206(4):327-335. doi: 10.1007/s00430-017-0506-1. Epub 2017 May 2.

Abstract

Adult T cell leukemia/lymphoma (ATLL) is a life-threatening malignancy of HTLV-1 infected Th lymphocytes. In the present study host-virus interactions were investigated by assessment of HTLV-1 proviral load (PVL) and host gene expression. A cross-sectional study was carried out on 18 ATLL, 10 HAM/TSP patients and 18 HTLV-1 asymptomatic carriers (ACs). DNA and mRNA of the peripheral blood mononuclear cells were extracted for PVL and LAT, BIM, c-FOS and RAD51 gene expression measurement using qRT-PCR. The mean PVL in ATLL patients was 11,430 ± 3770 copies/104 which was statistically higher than ACs, 530 ± 119 copies/104, (p < 0.001). The expression of BIM, and c-FOS in ATLL patients were higher than HTLV-1 ACs; however, there were no statistically significant differences. The expression of RAD51 as an essential player on DNA repair showed around 160 times increase in ATLL group (166 ± 95) compared to ACs (1.04 ± 0.34) which is statistically significant (p < 0.001). Interestingly, there was a positive correlation between RAD51 expression and HTLV-PVL. The expression of LAT as a central adaptor in TCR signaling interestingly was around 36 times higher in ATLL group than ACs (ATLL; 41.33 ± 19.91 vs. ACs; 1.15 ± 0.22, p < 0.001). This finding showed that TCR signaling pathway mainly provides the growth factors for transformed cells. Furthermore, the overexpression of RAD51 which has been induced in HTLV-1 infected cells as a consequence of virus replication is not able to overcome the DNA damage toward cell transformation.

Keywords: ATLL; BIM; HTLV-1 proviral load; LAT; RAD51; c-FOS.

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis*
  • Adult
  • Bcl-2-Like Protein 11 / analysis*
  • Cross-Sectional Studies
  • Female
  • Gene Expression Profiling
  • Human T-lymphotropic virus 1 / isolation & purification*
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / pathology*
  • Leukemia-Lymphoma, Adult T-Cell / virology
  • Leukocytes, Mononuclear / pathology
  • Leukocytes, Mononuclear / virology
  • Male
  • Membrane Proteins / analysis*
  • Middle Aged
  • Proto-Oncogene Proteins c-fos / analysis*
  • Proviruses / isolation & purification
  • Rad51 Recombinase / analysis*
  • Viral Load*

Substances

  • Adaptor Proteins, Signal Transducing
  • Bcl-2-Like Protein 11
  • LAT protein, human
  • Membrane Proteins
  • Proto-Oncogene Proteins c-fos
  • RAD51 protein, human
  • Rad51 Recombinase