Co-dependence of HTLV-1 p12 and p8 Functions in Virus Persistence

• DOI: 10.1371/journal.ppat.1004454
• Publication Date: 2014-11-06T19:39:02Z
• Authors: Cynthia A. Pise-M...; Maria Fernanda de...; Yoshimi Enose-Aka...; R. Cody Buchmann; Claudio Fenizia; Robyn Washington ...; Dustin Edwards; Martina Fiocchi; Luiz Carlos Alcan...; Izabela Bialuk; Jhanelle Graham; Jean-Claude Walser; Katherine McKinnon; Bernardo Galvão-C...; Antoine Gessain; David Venzon; Steven Jacobson; Genoveffa Franchini
• Keywords: Infectivity; Seroconversion; Viremia

HTLV-1 orf-I is linked to immune evasion, viral replication and persistence. Examining the sequence of 160 HTLV-1-infected individuals; we found polymorphism that alters relative amounts p12 its cleavage product p8. Three groups were identified on basis p8 expression: predominantly p12, balanced expression We a significant association between with high DNA loads, correlate disease development. To determine individual roles in persistence, constructed infectious molecular clones expressing (D26), (G29S) or (N26). As previously showed, cells N26 had higher level virus transmission vitro. However, when inoculated into Rhesus macaques, producing caused only partial seroconversion 3 4 animals 1 those was positive by PCR. None exposed G29S seroconverted detectable DNA. In contrast, D26 vitro studies THP-1 suggested sufficient for productive infection monocytes. Since plays role T-cell activation recognition; compared CTL response elicited CD4+ T-cells infected different clones. Although supernatant p19 levels loads all four lines similar, difference Tax-specific HLA.A2-restricted killing observed. Cells Orf-I-knockout (12KO), killed CTLs, whereas resistant killing. These results indicate efficient persistence spread require combined functions