Cell Cycle Changes, DNA Ploidy, and PTTG1 Gene Expression in HTLV-1 Patients

Author(s)

Levy, Debora ^[1] ; Ferreira, Mari Cleia M. R. ^[2] ; Reichert, Cadiele O. ^[1] ; de Almeida, Lis Vilela ^[2] ; Brocardo, Graciela ^[2] ; Lage, Luis Alberto P. C. ^[2] ; Culler, Hebert F. ^[2] ; Nukui, Youko ^[3] ; Bydlowski, Sergio P. ^[1] ; Pereira, Juliana ^[4]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Immunol LIM19, Lipids Oxidat & Cell Biol Team, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Hematol Hemotherapy & Cell Therapy, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Prosangue Fdn, Sch Med, Dept Hematol Hemotherapy & Cell Therapy, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Lab Med Invest Pathogenesis & Targeted Therapy On, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN MICROBIOLOGY; v. 11, JUL 24 2020.
• Web of Science Citations: 0

Abstract

Human T-cell lymphotropic virus type-1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). Genetic instability is the hallmark of ATL. Cell cycle progression is needed for virus particle reproduction. HTLV-1 encoded Tax protein ultimately disrupts the mitotic spindle checkpoint, leading to incorrect chromosome segregation, resulting in aneuploidy. Cell cycle abnormalities have been described in T cells transfected with HTLV-1 virusin vitro, but not in HTLV-1 asymptomatic carriers. PTTG1 and HTLV-1 viral protein Tax exhibit a cooperative transforming activity. Overexpressed PTTG1 results in chromosome instability and aneuploidy, which has been suggested as a mechanism underlying PTTG1 transforming activity. Here we aimed to investigate cell cycle, DNA ploidy and PTTG1 mRNA expression in CD4(+)and CD8(+)T cells in healthy subjects (HS), HTLV-1 asymptomatic carriers and ATL patients. We have identified that HTLV-1 asymptomatic carriers have shown DNA aneuploidy and cell cycle arrest at cell cycle phase G(0)/G(1)in CD4(+)T cells. CD8(+)T cells of HTLV-1 asymptomatic carriers also demonstrated DNA aneuploidy but without alteration in cell cycle. In ATL, CD4(+)and CD8(+)T cells present a higher number of cells in cell cycle S-phase and PTTG1 overexpression. These studies provide insight into malignant transformation of HTLV-1 asymptomatic carriers to ATL patients. (AU)

• FAPESP's process: 11/22132-0 - Analysis of the hsecurin gene expression and DNA index in HTLV-1 carriers and patients with leukemia-lymphoma T-cell adult as markers of progression disease
• Grantee: Juliana Pereira
• Support Opportunities: Regular Research Grants