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  • Meeting abstract
  • Open Access

The reverse genetics of HTLV-1 infected patients

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Retrovirology20118 (Suppl 1) :A193

  • Published:


  • Viral Replication
  • Genetic Variability
  • Transmission Rate
  • Transmembrane Domain
  • Infected Patient

The HTLV-1 ORF-1-encoded p12 protein induces T-cell activation and proliferation, while the cleaved p8 protein downregulates TCR signaling. In this study, we investigated whether there is a correlation between genetic variation within ORF-1 and the clinical status or proviral load in HTLV-1 infected individuals. The ORF-1 gene was amplified by PCR from PBMCs of 163 HTLV-1-infected patients (85 carriers, 78 HAM/TSP) from different geographical regions and a total of 1,640 clones were sequenced. The majority of the patients (73%) carried mutations in ORF-1 that resulted in the expression of more p12 than p8 (50% Carriers and 50% HAM/TSP). The highest genetic variability within ORF-1 was found in the two transmembrane domains of the protein. Of interest, a subclass of mutations was found more frequently in HAM/TSP patients compared to Carriers. While higher proviral loads were found in HAM/TSP patients compared to Carriers (p=0.0001), no correlation between proviral load and the ORF-1 isoform expressed was observed (mainly p12, both p12 and p8, or mainly p8). Currently experiments are aimed at determining the significance of these mutations in ORF-1 function in regard to T-cell activation and proliferation. In addition, mutations will be characterized for their role in viral infectivity and transmission rates ex vivo and in a rhesus macaque model. Determining the effects of ORF-1 mutants on viral replication, spread and latency will provide insight into the pathogenesis of HTLV-1 infection.

Authors’ Affiliations

Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
Oswaldo Cruz Foundation Salvador, Bahia, Brazil
HTLV Center/ Bahia School of Medicine and Public Health, Salvador, Bahia, Brazil
Department of General and Experimental Pathology, Medical University of Białystok, Białystok, 15-222, Poland
Unité de Virologie Humaine, Département de Biologie, Ecole Normale Supérieure Lyon, Lyon, France
Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA
Unité d’Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, France


© Alcantara et al; licensee BioMed Central Ltd. 2011

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.