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https://www.arca.fiocruz.br/handle/icict/10386
CO-DEPENDENCE OF HTLV-1 P12 AND P8 FUNCTIONS IN VIRUS PERSISTENCE.
Author
Masison, Cynthia A. Pise
Amarante, Maria Fernanda de Castro
Akahata, Yoshimi Enose
Buchmann, R. Cody
Fenizia, Claudio
Parks, Robyn Washington
Edwards, Dustin
Fiocchi, Martina
Alcantara, Luiz Carlos Júnior
Bialuk, Izabela
Graham, Jhanelle
Walser, Jean-Claude
McKinnon, Katherine
Castro Filho, Bernardo Galvão
Gessain, Antoine
Venzon, David
Jacobson, Steven
Franchini, Genoveffa
Amarante, Maria Fernanda de Castro
Akahata, Yoshimi Enose
Buchmann, R. Cody
Fenizia, Claudio
Parks, Robyn Washington
Edwards, Dustin
Fiocchi, Martina
Alcantara, Luiz Carlos Júnior
Bialuk, Izabela
Graham, Jhanelle
Walser, Jean-Claude
McKinnon, Katherine
Castro Filho, Bernardo Galvão
Gessain, Antoine
Venzon, David
Jacobson, Steven
Franchini, Genoveffa
Affilliation
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Institute of Neurological Disorders and Stroke. Viral Immunology Section, Neuroimmunology Branch. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Medical University in Białystok. Department of General and Experimental Pathology. Białystok, Poland
National Institute of Neurological Disorders and Stroke. Viral Immunology Section, Neuroimmunology Branch. Bethesda, Maryland, USA
University of Basel. Evolutionary Biology, Genetic Diversity Centre. Basel, Switzerland
National Institutes of Health. National Cancer Institute. Vaccine Branch Flow Cytometry Core Laboratory. Bethesda, Maryland, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Institut Pasteur. Unité d’Epidémiologie et Physiopathologie des Virus Oncogènes. De´partement de Virologie, Batiment Lwoff. Paris, France
National Cancer Institute. Biostatistics and Data Management Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Institute of Neurological Disorders and Stroke. Viral Immunology Section, Neuroimmunology Branch. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Medical University in Białystok. Department of General and Experimental Pathology. Białystok, Poland
National Institute of Neurological Disorders and Stroke. Viral Immunology Section, Neuroimmunology Branch. Bethesda, Maryland, USA
University of Basel. Evolutionary Biology, Genetic Diversity Centre. Basel, Switzerland
National Institutes of Health. National Cancer Institute. Vaccine Branch Flow Cytometry Core Laboratory. Bethesda, Maryland, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Institut Pasteur. Unité d’Epidémiologie et Physiopathologie des Virus Oncogènes. De´partement de Virologie, Batiment Lwoff. Paris, France
National Cancer Institute. Biostatistics and Data Management Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
National Cancer Institute. Animal Models and Retroviral Vaccines Section. Bethesda, Maryland, USA
Abstract
HTLV-1 orf-I is linked to immune evasion, viral replication and persistence. Examining the orf-I sequence of 160 HTLV-1-
infected individuals; we found polymorphism of orf-I that alters the relative amounts of p12 and its cleavage product p8.
Three groups were identified on the basis of p12 and p8 expression: predominantly p12, predominantly p8 and balanced
expression of p12 and p8. We found a significant association between balanced expression of p12 and p8 with high viral
DNA loads, a correlate of disease development. To determine the individual roles of p12 and p8 in viral persistence, we
constructed infectious molecular clones expressing p12 and p8 (D26), predominantly p12 (G29S) or predominantly p8 (N26).
As we previously showed, cells expressing N26 had a higher level of virus transmission in vitro. However, when inoculated
into Rhesus macaques, cells producing N26 virus caused only a partial seroconversion in 3 of 4 animals and only 1 of those
animals was HTLV-1 DNA positive by PCR. None of the animals exposed to G29S virus seroconverted or had detectable viral
DNA. In contrast, 3 of 4 animals exposed to D26 virus seroconverted and were HTLV-1 positive by PCR. In vitro studies in
THP-1 cells suggested that expression of p8 was sufficient for productive infection of monocytes. Since orf-I plays a role in Tcell
activation and recognition; we compared the CTL response elicited by CD4+ T-cells infected with the different HTLV-1
clones. Although supernatant p19 levels and viral DNA loads for all four infected lines were similar, a significant difference in
Tax-specific HLA.A2-restricted killing was observed. Cells infected with Orf-I-knockout virus (12KO), G29S or N26 were killed
by CTLs, whereas cells infected with D26 virus were resistant to CTL killing. These results indicate that efficient viral
persistence and spread require the combined functions of p12 and p8.
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