Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles.
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.
Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
Jane
J
Murphy
Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
William W
WW
Hall
Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
Lee
L
Ratner
Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
Noreen
N
Sheehy
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005110:Extracellular Space / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D015490:HTLV-I Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D015367:Human T-lymphotropic virus 2 / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D050779:Nuclear Factor 90 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D021381:Protein Transport; D034622:RNA Interference; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin; D020079:Terminal Repeat Sequences; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D014779:Virus Replication
C107489:BIRC5 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; C479751:HBZ protein, human T-cell leukemia virus type I; C429643:ILF3 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008562:Membrane Glycoproteins; D050779:Nuclear Factor 90 Proteins; D012191:Retroviridae Proteins; D000077022:Survivin; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases
APH-2; HBZ; HTLV; NFAR; Survivin; Tax1; Tax2; YM155