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

Retrovirology

Noreen Sheehy¹  William W Hall¹  Terence N Bukong¹  Áine McCabe¹  Céline Marban² 

[1] Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland;Inserm U977, Faculté de Chirurgie Dentaire, 1 Place de l'Hôpital, 67000, Strasbourg, France

关键词: Jun;    AP-1;    Tax2;    APH-2;    HTLV-2;   

Others  :  1209227
DOI  :  10.1186/1742-4690-9-98

 received in 2012-02-24, accepted in 2012-11-18,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Marban et al.; licensee BioMed Central Ltd.

【 图 表 】

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