Silencers of HTLV-1 and HTLV-2: the pX-encoded latency-maintenance factors.
Retrovirology
; 16(1): 25, 2019 09 06.
Article
en En
| MEDLINE
| ID: mdl-31492165
ABSTRACT
Of the members of the primate T cell lymphotropic virus (PTLV) family, only the human T-cell leukemia virus type-1 (HTLV-1) causes disease in humans-as the etiological agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other auto-inflammatory disorders. Despite having significant genomic organizational and structural similarities, the closely related human T-cell lymphotropic virus type-2 (HTLV-2) is considered apathogenic and has been linked with benign lymphoproliferation and mild neurological symptoms in certain infected patients. The silencing of proviral gene expression and maintenance of latency are central for the establishment of persistent infections in vivo. The conserved pX sequences of HTLV-1 and HTLV-2 encode several ancillary factors which have been shown to negatively regulate proviral gene expression, while simultaneously activating host cellular proliferative and pro-survival pathways. In particular, the ORF-II proteins, HTLV-1 p30II and HTLV-2 p28II, suppress Tax-dependent transactivation from the viral promoter-whereas p30II also inhibits PU.1-mediated inflammatory-signaling, differentially augments the expression of p53-regulated metabolic/pro-survival genes, and induces lymphoproliferation which could promote mitotic proviral replication. The ubiquitinated form of the HTLV-1 p13II protein localizes to nuclear speckles and interferes with recruitment of the p300 coactivator by the viral transactivator Tax. Further, the antisense-encoded HTLV-1 HBZ and HTLV-2 APH-2 proteins and mRNAs negatively regulate Tax-dependent proviral gene expression and activate inflammatory signaling associated with enhanced T-cell lymphoproliferation. This review will summarize our current understanding of the pX latency-maintenance factors of HTLV-1 and HTLV-2 and discuss how these products may contribute to the differences in pathogenicity between the human PTLVs.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Virus Linfotrópico T Tipo 1 Humano
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Virus Linfotrópico T Tipo 2 Humano
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Latencia del Virus
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Proteínas Reguladoras y Accesorias Virales
Límite:
Humans
Idioma:
En
Revista:
Retrovirology
Asunto de la revista:
VIROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos