Interplay between the HTLV-2 Tax and APH-2 proteins in the regulation of the AP-1 pathway

• Published in: Retrovirology Vol. 9; no. 1; p. 98
• Main Authors: Marban, Céline, McCabe, Aine, Bukong, Terence N, Hall, William W, Sheehy, Noreen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03-12-2012; BioMed Central; BMC
• Subjects: Activator protein 1; Amino acids; Amyloid Precursor Protein Secretases - metabolism; Antisense; AP-1; APH-2; c-Jun protein; Collagenases - genetics; Development and progression; Experiments; Gene Expression Regulation; Gene Products, tax - metabolism; Genes; Genetic aspects; Genetic research; Genetic transcription; Genomes; Genomics; HTLV-2; HTLV-II (Virus); Human health and pathology; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Human T-lymphotropic virus 2 - metabolism; Humans; Immune system; Infectious diseases; Jun; JunB protein; Leukemia; Life cycle; Life Sciences; Lymphocytes T; Membrane Glycoproteins - metabolism; Pathogenesis; Physiological aspects; Promoter Regions, Genetic; Protein Binding; Protein Interaction Domains and Motifs; Protein Transport; Proteins; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Regulation; regulatory proteins; Signal Transduction; Studies; T cells; Tax2; Transcription; Transcription Factor AP-1 - metabolism; Transcription factors; Transcription, Genetic; Transcriptional Activation; University colleges; Viral proteins; France; Ireland; Tax2; Jun; HTLV-2; AP-1; APH-2
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/1742-4690-9-98

In contrast with human T-cell leukemia virus type 1 (HTLV-1) that causes ATL (adult T-cell leukemia), HTLV-2 has not been causally linked to malignant disease. The minus strand of the HTLV genomes encode the regulatory proteins HTLV-1 bZIP factor (HBZ) for HTLV-1 and antisense protein of HTLV-2 (APH-2) for HTLV-2. Unlike the viral proteins Tax1 and Tax2, both HBZ and APH-2 are constitutively expressed in infected cells suggesting that they may play important roles in the pathogenesis of these viruses. To date, very little is known about the function of APH-2 except that it inhibits Tax2-mediated transcription of HTLV-2 genes. In the present study, we investigated the role of APH-2 in basal and Tax2B-mediated activation of the AP-1 pathway.
We demonstrate that, unlike HBZ, APH-2 stimulates basal AP-1 transcription by interacting with c-Jun and JunB through its non-conventional bZIP domain. In addition, when Tax2 and APH-2 are co-expressed, they physically interact in vivo and in vitro and APH-2 acts as an inhibitor of Tax2-mediated activation of AP-1 transcription.
This report is the first to document that HTLV-2 can modulate the AP-1 pathway. Altogether our results reveal that, in contrast with HBZ, APH-2 regulates AP-1 activity in a Tax2-dependant manner. As the AP-1 pathway is involved in numerous cellular functions susceptible to affect the life cycle of the virus, these distinct biological properties between HBZ and APH-2 may contribute to the differential pathogenic potential of HTLV-1 and HTLV-2.