Interplay between the HTLV-2 Tax and APH-2 proteins in the regulation of the AP-1 pathway
dc.contributor.author | Marban, Céline | |
dc.contributor.author | McCabe, Áine | |
dc.contributor.author | Bukong, Terence N | |
dc.contributor.author | Hall, William W | |
dc.contributor.author | Sheehy, Noreen | |
dc.date.accessioned | 2013-01-02T16:06:15Z | |
dc.date.available | 2013-01-02T16:06:15Z | |
dc.date.issued | 2012-12-03 | |
dc.identifier.citation | Retrovirology. 2012 Dec 03;9(1):98 | |
dc.identifier.uri | http://dx.doi.org/10.1186/1742-4690-9-98 | |
dc.identifier.uri | http://hdl.handle.net/10147/264017 | |
dc.description.abstract | Abstract Background 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. Results 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. Conclusions 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. | |
dc.title | Interplay between the HTLV-2 Tax and APH-2 proteins in the regulation of the AP-1 pathway | |
dc.type | Journal Article | |
dc.language.rfc3066 | en | |
dc.rights.holder | Céline Marban et al.; licensee BioMed Central Ltd. | |
dc.description.status | Peer Reviewed | |
dc.date.updated | 2012-12-27T20:07:24Z | |
refterms.dateFOA | 2018-08-23T03:22:15Z | |
html.description.abstract | Abstract Background 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. Results 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. Conclusions 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. |