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

Hdl Handle:
http://hdl.handle.net/10147/264017
Title:
Interplay between the HTLV-2 Tax and APH-2 proteins in the regulation of the AP-1 pathway
Authors:
Marban, Céline; McCabe, Áine; Bukong, Terence N; Hall, William W; Sheehy, Noreen
Citation:
Retrovirology. 2012 Dec 03;9(1):98
Issue Date:
3-Dec-2012
URI:
http://dx.doi.org/10.1186/1742-4690-9-98; http://hdl.handle.net/10147/264017
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.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorMarban, Céline-
dc.contributor.authorMcCabe, Áine-
dc.contributor.authorBukong, Terence N-
dc.contributor.authorHall, William W-
dc.contributor.authorSheehy, Noreen-
dc.date.accessioned2013-01-02T16:06:15Z-
dc.date.available2013-01-02T16:06:15Z-
dc.date.issued2012-12-03-
dc.identifier.citationRetrovirology. 2012 Dec 03;9(1):98-
dc.identifier.urihttp://dx.doi.org/10.1186/1742-4690-9-98-
dc.identifier.urihttp://hdl.handle.net/10147/264017-
dc.description.abstractAbstract 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.titleInterplay between the HTLV-2 Tax and APH-2 proteins in the regulation of the AP-1 pathway-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderCéline Marban et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2012-12-27T20:07:24Z-
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