Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles

Autor: Noreen Sheehy, William W. Hall, Jane L Murphy, Lee Ratner
Rok vydání: 2016
Předmět:
Transcriptional Activation
0301 basic medicine
Protein family
Survivin
viruses
Protein domain
Retroviridae Proteins
Virus Replication
Article
Cell Line
Inhibitor of Apoptosis Proteins
03 medical and health sciences
RNA interference
Two-Hybrid System Techniques
Virology
Protein Interaction Mapping
Humans
Protein Interaction Domains and Motifs
Nuclear Factor 90 Proteins
Human T-lymphotropic virus 1
Membrane Glycoproteins
biology
Human T-lymphotropic virus 2
Terminal Repeat Sequences
RNA
biology.organism_classification
HTLV-I Infections
Transport protein
Protein Transport
Basic-Leucine Zipper Transcription Factors
030104 developmental biology
Gene Expression Regulation
Viral replication
Gene Knockdown Techniques
Host-Pathogen Interactions
RNA Interference
Amyloid Precursor Protein Secretases
Extracellular Space
Protein Binding
Zdroj: Virology. 494:129-142
ISSN: 0042-6822
DOI: 10.1016/j.virol.2016.04.012
Popis: The human T-cell leukaemia virus type 1 and type 2 (HTLV-1/HTLV-2) antisense proteins HBZ and APH-2 play key roles in the HTLV lifecycles and persistence in the host. Nuclear Factors Associated with double-stranded RNA (NFAR) proteins NF90/110 function in the lifecycles of several viruses and participate in host innate immunity against infection and oncogenesis. Using GST pulldown and co-immunoprecipitation assays we demonstrate specific novel interactions between HBZ/APH-2 and NF90/110 and characterised the protein domains involved. Moreover we show that NF90/110 significantly enhance Tax mediated LTR activation, an effect that was abolished by HBZ but enhanced by APH-2. Additionally we found that HBZ and APH-2 modulate the promoter activity of survivin and are capable of antagonising NF110-mediated survivin activation. Thus interactions between HTLV antisense proteins and the NFAR protein family have an overall positive impact on HTLV infection. Hence NFARs may represent potential therapeutic targets in HTLV infected cells.
Databáze: OpenAIRE
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