RESUMO
In a perspective of a comparative virology approach, characterization of the bovine leukemia virus (BLV) model may be helpful to better understand infection by the related human T-lymphotropic virus type 1 (HTLV-1). In this paper, we first provide detailed protocols to inoculate cloned BLV proviruses into sheep or cattle. We also describe methods to quantify apoptosis ex vivo and cell turnover in vivo.
Assuntos
Leucose Enzoótica Bovina/metabolismo , Vírus da Leucemia Bovina/metabolismo , Modelos Biológicos , Animais , Apoptose , Bovinos , Leucose Enzoótica Bovina/patologia , Vírus Linfotrópico T Tipo 1 Humano , Humanos , OvinosRESUMO
Different animal models have been proposed to investigate the mechanisms of Human T-lymphotropic Virus (HTLV)-induced pathogenesis: rats, transgenic and NOD-SCID/γcnull (NOG) mice, rabbits, squirrel monkeys, baboons and macaques. These systems indeed provide useful information but have intrinsic limitations such as lack of disease relevance, species specificity or inadequate immune response. Another strategy based on a comparative virology approach is to characterize a related pathogen and to speculate on possible shared mechanisms. In this perspective, bovine leukemia virus (BLV), another member of the deltaretrovirus genus, is evolutionary related to HTLV-1. BLV induces lymphoproliferative disorders in ruminants providing useful information on the mechanisms of viral persistence, genetic determinants of pathogenesis and potential novel therapies.
Assuntos
Interações Hospedeiro-Patógeno , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Vírus da Leucemia Bovina/fisiologia , Animais , Pesquisa Biomédica/tendências , Modelos Animais de Doenças , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Humanos , Vírus da Leucemia Bovina/patogenicidade , Virologia/tendênciasRESUMO
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes cancer (Adult T cell Leukemia, ATL) and a spectrum of inflammatory diseases (mainly HTLV-associated myelopathy-tropical spastic paraparesis, HAM/TSP). Since virions are particularly unstable, HTLV-1 transmission primarily occurs by transfer of a cell carrying an integrated provirus. After transcription, the viral genomic RNA undergoes reverse transcription and integration into the chromosomal DNA of a cell from the newly infected host. The virus then replicates by either one of two modes: (i) an infectious cycle by virus budding and infection of new targets and (ii) mitotic division of cells harboring an integrated provirus. HTLV-1 replication initiates a series of mechanisms in the host including antiviral immunity and checkpoint control of cell proliferation. HTLV-1 has elaborated strategies to counteract these defense mechanisms allowing continuous persistence in humans.
Assuntos
Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Animais , Infecções por HTLV-I/transmissão , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Modelos Biológicos , Proteínas Virais/genética , Proteínas Virais/metabolismo , Replicação ViralRESUMO
Attenuation of p53 activity appears to be a major step in Human T-lymphotropic virus type 1 (HTLV-1) Tax transformation. However, p53 genomic mutations are late and rather infrequent events in HTLV-1 induced Adult T cell leukemia (ATL). The paper by Zane et al. shows that a mediator of p53 activity, Wild-type p53-induced phosphatase 1 (Wip1), contributes to Tax-induced oncogenesis in a mouse model. Wip1 may therefore be a novel target for therapeutic approaches.
