Clonality of HTLV-2 in natural infection

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POSTER PRESENTATION Open Access Clonality of HTLV-2 in natural infection Anat Melamed 1* , Aviva D Witkover 1 , Rachael Brown 1 , Kristin Ladell 2 , Niall Gormley 3 , Edward L Murphy 4 , Graham P Taylor 5 , David A Price 2 , Charles RM Bangham 1 From 16th International Conference on Human Retroviruses: HTLV and Related Viruses Montreal, Canada. 26-30 June 2013 We recently developed a high-throughput sequencing method for analysis and quantification of HTLV-1 inte- gration sites in the host genome (Gillet et al, 2011, Blood). Using this method we investigated the effect of the genomic environment on integration targeting, clonal expansion and spontaneous HTLV-1 proviral expression (Gillet et al, 2011, Blood, Melamed et al, 2013, PLoS Pathogens). HTLV-2 preferentially infects CD8+ T cells, with a minority of the proviral load in CD4+ T cells. Here we describe the use of our high-throughput techni- que to investigate the distribution of HTLV-2 proviral integration sites in the host genome, in peripheral blood mononuclear cell (PBMC) DNA of HTLV-2 infected individuals (n=28). We also mapped and quantified pro- viral integration sites separately in flow-sorted CD4 +CD8- and CD4-CD8+ populations. We quantified the clone frequency distribution and clonal survival over time in 10 individuals, using samples from 2 time points sepa- rated by a median of 10 years. The results show that the clone frequency distribution of HTLV-2 in PBMCs is dis- tinct from that of HTLV-1 and resembles that of HTLV- 1-infected CD8+ T cells. These results suggest that in both HTLV-1 and HTLV-2 infections, there is a greater degree of selective oligoclonal clonal expansion in infected CD8+ T cells than in CD4+ T cells. We are now investigating the selection forces that underlie this dichot- omy between T cell lineages. Authorsdetails 1 Section of Immunology, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, UK. 2 Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, UK. 3 Illumina, Chesterford Research Park, Essex, Little Chesterford, UK. 4 University of California San Francisco, California, USA. 5 Section of Infectious Diseases, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, UK. Published: 7 January 2014 doi:10.1186/1742-4690-11-S1-P138 Cite this article as: Melamed et al.: Clonality of HTLV-2 in natural infection. Retrovirology 2014 11(Suppl 1):P138. Submit your next manuscript to BioMed Central and take full advantage of: Convenient online submission Thorough peer review No space constraints or color figure charges Immediate publication on acceptance Inclusion in PubMed, CAS, Scopus and Google Scholar Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit 1 Section of Immunology, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, UK Full list of author information is available at the end of the article Melamed et al. Retrovirology 2014, 11(Suppl 1):P138 http://www.retrovirology.com/content/11/S1/P138 © 2014 Melamed et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Transcript of Clonality of HTLV-2 in natural infection

POSTER PRESENTATION Open Access

Clonality of HTLV-2 in natural infectionAnat Melamed1*, Aviva D Witkover1, Rachael Brown1, Kristin Ladell2, Niall Gormley3, Edward L Murphy4,Graham P Taylor5, David A Price2, Charles RM Bangham1

From 16th International Conference on Human Retroviruses: HTLV and Related VirusesMontreal, Canada. 26-30 June 2013

We recently developed a high-throughput sequencingmethod for analysis and quantification of HTLV-1 inte-gration sites in the host genome (Gillet et al, 2011,Blood). Using this method we investigated the effect ofthe genomic environment on integration targeting, clonalexpansion and spontaneous HTLV-1 proviral expression(Gillet et al, 2011, Blood, Melamed et al, 2013, PLoSPathogens). HTLV-2 preferentially infects CD8+ T cells,with a minority of the proviral load in CD4+ T cells.Here we describe the use of our high-throughput techni-que to investigate the distribution of HTLV-2 proviralintegration sites in the host genome, in peripheral bloodmononuclear cell (PBMC) DNA of HTLV-2 infectedindividuals (n=28). We also mapped and quantified pro-viral integration sites separately in flow-sorted CD4+CD8- and CD4-CD8+ populations. We quantified theclone frequency distribution and clonal survival over timein 10 individuals, using samples from 2 time points sepa-rated by a median of 10 years. The results show that theclone frequency distribution of HTLV-2 in PBMCs is dis-tinct from that of HTLV-1 and resembles that of HTLV-1-infected CD8+ T cells. These results suggest that inboth HTLV-1 and HTLV-2 infections, there is a greaterdegree of selective oligoclonal clonal expansion ininfected CD8+ T cells than in CD4+ T cells. We are nowinvestigating the selection forces that underlie this dichot-omy between T cell lineages.

Authors’ details1Section of Immunology, Imperial College London, Wright-Fleming Institute,Norfolk Place, London, UK. 2Institute of Infection and Immunity, CardiffUniversity School of Medicine, Cardiff, Wales, UK. 3Illumina, ChesterfordResearch Park, Essex, Little Chesterford, UK. 4University of California SanFrancisco, California, USA. 5Section of Infectious Diseases, Imperial CollegeLondon, Wright-Fleming Institute, Norfolk Place, London, UK.

Published: 7 January 2014

doi:10.1186/1742-4690-11-S1-P138Cite this article as: Melamed et al.: Clonality of HTLV-2 in naturalinfection. Retrovirology 2014 11(Suppl 1):P138.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submit

1Section of Immunology, Imperial College London, Wright-Fleming Institute,Norfolk Place, London, UKFull list of author information is available at the end of the article

Melamed et al. Retrovirology 2014, 11(Suppl 1):P138http://www.retrovirology.com/content/11/S1/P138

© 2014 Melamed et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.