Evaluation of INOS, ICAM-1, and VCAM-1 gene expression: A study of adult T cell leukemia malignancy associated with HTLV-1

Arch Virol. 2017 Apr;162(4):1009-1015. doi: 10.1007/s00705-016-3213-0. Epub 2017 Jan 21.

Abstract

The main aim of this study was to evaluate the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and inducible nitric oxide synthase (iNOS) as host factors, and proviral load as the viral parameter, in adult T-cell leukemia/lymphoma (ATLL) individuals and healthy carrier (HC(s)) groups. Peripheral blood mononuclear cells (PBMC) from ATLL patients (n = 17) and HC subjects (as the control group, n = 17) were evaluated using real-time PCR to determine the levels of HTLV-1 proviral load and mRNA expression of ICAM, VCAM-1, and iNOS. ICAM-1 was significantly lower in ATLL patients than in control subjects. Although the expression of VCAM-1 was higher in ATLL individuals, there was no significant difference between the studied groups. In addition, no iNOS expression was found in ATLL patients, when compared to the HCs subjects, while ATLL patients demonstrated a higher level of proviral load when compared to the control group. Considering the importance of ICAM-1 in facilitating immune recognition of infected cells, it is posited that reduction of ICAM-1 expression is a unique strategy for circumventing appropriate immune responses that are mediated by different accessory proteins. Additionally, as the viral regulatory protein Tax and the NF-κB pathway play pivotal roles in expression of iNOS, lack of the latter in ATLL patients may be related to the level of Tax expression, disruption of the NF-κB pathway, or the occurrence of epigenetical mechanisms in the human iNOS promoter. Further studies are recommended to gain a better understanding of the interaction between host and viral factors in HTLV-1 pathogenesis and to identify a possible therapeutic target for ATLL.

MeSH terms

  • Adult
  • Female
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Leukemia-Lymphoma, Adult T-Cell / metabolism
  • Leukemia-Lymphoma, Adult T-Cell / virology
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type II / genetics*
  • Nitric Oxide Synthase Type II / metabolism
  • Promoter Regions, Genetic
  • Vascular Cell Adhesion Molecule-1 / genetics*
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II