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

Autor: Debora Levy, Mari Cleia M. R. Ferreira, Cadiele O. Reichert, Lis Vilela de Almeida, Graciela Brocardo, Luis Alberto P. C. Lage, Hebert F. Culler, Youko Nukui, Sergio P. Bydlowski, Juliana Pereira
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Frontiers in Microbiology, Vol 11 (2020)
Druh dokumentu: article
ISSN: 1664-302X
DOI: 10.3389/fmicb.2020.01778
Popis: 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 virus in 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 G0/G1 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.
Databáze: Directory of Open Access Journals