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  • Oral presentation
  • Open Access

Functional comparison of the HTLV-1 and HTLV-2 antisense viral proteins: implications for pathogenesis

  • 1, 2,
  • 1, 2,
  • 1, 2 and
  • 1, 2, 3, 4Email author
Retrovirology201512 (Suppl 1) :O8

  • Published:


  • Cellular Pathway
  • Proviral Load
  • Viral Persistence
  • Basic Leucine Zipper
  • mRNA Copy Number

HTLV-1 and HTLV-2 are highly related retroviruses that transform T-lymphocytes in cell culture, but display distinct pathobiology in vivo. HTLV-1 is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL) and a neurodegenerative disease (HAM/TSP), whereas HTLV-2 is nonpathogenic. HTLV-1 encodes a protein on the antisense strand of its proviral genome called HTLV-1 basic leucine zipper (bZIP) factor (HBZ), which inhibits Tax-mediated viral transcription and is required for high proviral load and efficient viral persistence. Studies have shown that HBZ also modulates several cellular pathways that include activating protein-1 (AP-1), NF-κB, and innate immune responses. HTLV-2 also encodes a protein on the antisense genome strand named antisense protein of HTLV-2 (APH-2). Like HBZ, APH-2 also inhibits Tax-mediated viral transcription. However, we show that unlike HBZ, loss of APH-2 results in enhanced viral replication and viral persistence in infected rabbits. This led us to hypothesize that HBZ and APH-2 modulate cellular pathways differently, which translates to the distinct HTLV-1 and HTLV-2 pathobiology. In this study we directly compared APH-2 and HBZ biologic properties and functions on known HBZ-modulated pathways. We provide evidence that APH-2 protein is significantly less stable than HBZ protein (half-life approximately 30m vs. 6.5h). Despite the difference in protein half-life, HTLV-2 does not compensate for this instability by increasing APH-2 mRNA copy number. Additionally, APH-2 and HBZ share similar mRNA stability measurements. We further show that APH-2 inhibits the transforming growth factor β (TGF-β) signaling pathway in contrast to HBZ's enhancement. Like HBZ, APH-2 is able to inhibit the cellular transcription factors p65 (NF-κB) and interferon response factor (IRF)-1. Taken together our results indicate that APH-2 is limited in some functions it shares with HBZ. Further studies should focus on distinct HBZ functions and interacting pathways to find new potential therapeutic targets for HTLV-1 disease.

Authors’ Affiliations

Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA
Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA
Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA


© Panfil et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.