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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals
Philosophical Transactions of the Royal Society B: Biological Sciences, Volume 370, No. 1676, Year 2015
Notification
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Description
Advances in immunoglobulin (Ig) sequencing technology are leading to new perspectives on immune system dynamics. Much research in this nascent field has focused on resolving immune responses to viral infection. However, the dynamics of B-cell diversity in early HIV infection, and in response to antiretroviral therapy, are still poorly understood. Here, we investigate these dynamics through bulk Ig sequencing of samples collected over 2 years from a group of eight HIV-1 infected patients, five of whom received antiretroviral therapy during the first half of the study period. We applied previously published methods for visualizing and quantifying B-cell sequence diversity, including the Gini index, and compared their efficacy to alternative measures. While we found significantly greater clonal structure in HIVinfected patients versus healthy controls, within HIV patients, we observed no significant relationships between statistics of B-cell clonal expansion and clinical variables such as viral load and CD4+ count. Although there are many potential explanations for this,we suggest that important factors include poor sampling resolution and complex B-cell dynamics that are difficult to summarize using simple summary statistics. Importantly,we find a significant association between observed Gini indices and sequencing read depth, andwe conclude that more robust analytical methods and a closer integration of experimental and theoretical work is needed to further our understanding of B-cell repertoire diversity during viral infection. © 2015 The Authors.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4528418/bin/rstb20140241supp1.pdf
Authors & Co-Authors
Hoehn, Kenneth B.
United Kingdom, Oxford
University of Oxford
Gall, Astrid
United Kingdom, Hinxton
Wellcome Sanger Institute
Bashford-Rogers, Rachael J.M.
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Cambridge
University of Cambridge
Fidler, Sarah J.
United Kingdom, London
Imperial College London
Kaye, Steve
United Kingdom, London
Imperial College London
Weber, Jonathan N.
United Kingdom, London
Imperial College London
McClure, Myra Olga
United Kingdom, London
Imperial College London
Kellam, P.
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, London
Ucl Faculty of Medical Sciences
Pybus, Oliver George
United Kingdom, Oxford
University of Oxford
Breckenridge, Alasdair M.
Unknown Affiliation
Clayden, Polly
Unknown Affiliation
Conlon, Christopher P.
Unknown Affiliation
Conradie, Francesca M.
Unknown Affiliation
Kaldor, John M.
Unknown Affiliation
Maggiolo, Franco
Unknown Affiliation
Ssali, Francis N.
Unknown Affiliation
Cooper, David A.
Unknown Affiliation
Kaleebu, Pontiano
Unknown Affiliation
Ramjee, G.
Unknown Affiliation
Schechter, Martin T.
Unknown Affiliation
Tambussi, Giuseppe
Unknown Affiliation
Weber, Jeffrey S.
Unknown Affiliation
Fidler, S.
Unknown Affiliation
Babiker, Abdel G.
United Kingdom, Oxford
University of Oxford
Peto, Timothy E.A.
United Kingdom, London
Mrc Clinical Trials Unit
McLaren, Anne
United Kingdom, London
Mrc Clinical Trials Unit
Beral, Valerie
United Kingdom, London
Mrc Clinical Trials Unit
Chêne, Geneviève
United Kingdom, London
Mrc Clinical Trials Unit
Hakim, James Gita
United Kingdom, London
Mrc Clinical Trials Unit
Porter, Kholoud
United Kingdom, Oxford
University of Oxford
Thomason, Margaret J.
United Kingdom, Oxford
University of Oxford
Ewings, Fiona M.
United Kingdom, Oxford
University of Oxford
Gabriel, Michelle
United Kingdom, Oxford
University of Oxford
Johnson, Denise L.
United Kingdom, Oxford
University of Oxford
Thompson, K.
United Kingdom, Oxford
University of Oxford
Cursley, Adam
United Kingdom, Oxford
University of Oxford
Donegan, Katherine L.
United Kingdom, Oxford
University of Oxford
Fossey, E.
United Kingdom, Oxford
University of Oxford
Kelleher, Peter W.
United Kingdom, Oxford
University of Oxford
Lee, K.
United Kingdom, Oxford
University of Oxford
Murphy, B.
United Kingdom, Oxford
University of Oxford
Nock, D.
United Kingdom, Oxford
University of Oxford
Phillips, Rodney E.
United Kingdom, London
Imperial College London
Frater, John
United Kingdom, London
Imperial College London
Ohm-Laursen, Line
United Kingdom, London
Imperial College London
Robinson, Nicola
United Kingdom, London
Imperial College London
Goulder, Philip Jeremy Renshaw
United Kingdom, London
Imperial College London
Brown, Helen L.
United Kingdom, London
Imperial College London
McClure, Marcella A.
Unknown Affiliation
Bonsall, David G.
Unknown Affiliation
Erlwein, Otto W.
Unknown Affiliation
Helander, A.
Unknown Affiliation
Robinson, Mark James
Unknown Affiliation
Cook, Lucy B.M.
Unknown Affiliation
Adcock, G.
Unknown Affiliation
Ahmed, P.
Unknown Affiliation
Paton, Nicholas I.J.
Unknown Affiliation
Fidler, Sarah J.
Unknown Affiliation
Kelleher, Anthony D.
Australia, Sydney
St. Vincent's Hospital Sydney
Australia, Kensington
The Kirby Institute
Moore, Richard D.
Australia, Greenwich
Northside Clinic
McFarlane, Robert
Unknown Affiliation
Roth, Norman J.
Australia, Melbourne
Prahran Market Clinic
Finlayson, Robert J.
Unknown Affiliation
Tee, Bian Kiem
Australia, Melbourne
Centre Clinic
Read, Timothy H.R.
Australia, Melbourne
Western Sydney Sexual Health Centre
Kelly, Mark D.
Australia, Brisbane
Aids Medical Unit
Doong, Nicholas C.
Australia, Sydney
Burwood rd Practice
Bloch, Mark Theo
Australia, Sydney
Holdsworth House Medical Practice
Workman, Cassy
Australia, Sydney
Aids Research Initiative
Grey, Pat A.
Australia, Kensington
The Kirby Institute
Cooper, David A.
Australia, Kensington
The Kirby Institute
Lawr, M.
Australia, Kensington
The Kirby Institute
Schechter, Mauro T.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Merçon, Mônica
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Barbosa de Souza, Monica
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Beppu-Yoshida, Carina
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Grangeiro da Silva, Jose Roberto
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Sampaio Amaral, A.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Fernandes de Aguiar, D.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
de Fátima Melo, Maria
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Quaresma Garrido, R.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Tambussi, Giuseppe
Italy, Milan
Irccs Ospedale San Raffaele
Nozza, Silvia
Italy, Milan
Irccs Ospedale San Raffaele
Pogliaghi, Manuela
Italy, Milan
Irccs Ospedale San Raffaele
Chiappetta, Stefania
Italy, Milan
Irccs Ospedale San Raffaele
Della Torre, Liviana
Italy, Milan
Irccs Ospedale San Raffaele
Gasparotto, E.
Italy, Milan
Irccs Ospedale San Raffaele
D'Offizi, G.
Italy, Rome
Irccs Istituto Nazionale Malattie Infettive Lazzaro Spallanzani
Vlassi, Chrysoula
Italy, Rome
Irccs Istituto Nazionale Malattie Infettive Lazzaro Spallanzani
Corpolongo, Angela
Italy, Rome
Irccs Istituto Nazionale Malattie Infettive Lazzaro Spallanzani
Wood, Robin R.
South Africa, Cape Town
Desmond Tutu Health Foundation
Pitt, J.
South Africa, Cape Town
Desmond Tutu Health Foundation
Orrell, C.
South Africa, Cape Town
Desmond Tutu Health Foundation
Cilliers, F.
South Africa, Cape Town
Desmond Tutu Health Foundation
Croxford, R.
South Africa, Cape Town
Desmond Tutu Health Foundation
Middelkoop, Keren
South Africa, Cape Town
Desmond Tutu Health Foundation
Bekker, Linda-Gail Gail
South Africa, Cape Town
Desmond Tutu Health Foundation
Heiberg, Christie
South Africa, Cape Town
Desmond Tutu Health Foundation
Rees, Helen V.
South Africa, Johannesburg
University of the Witwatersrand
Palanee-Phillips, Thesla
South Africa, Johannesburg
University of the Witwatersrand
Stevens, Wendy Susan
South Africa, Johannesburg
Charlotte Maxeke Johannesburg Academic Hospital
Ingram, Charlotte
South Africa, Johannesburg
Charlotte Maxeke Johannesburg Academic Hospital
Majam, Mohammed
South Africa, Johannesburg
Charlotte Maxeke Johannesburg Academic Hospital
Papathanasopoulos, Maria
South Africa, Johannesburg
Charlotte Maxeke Johannesburg Academic Hospital
Ramjee, Gita A.
South Africa, Tygerberg
South African Medical Research Council
Gappoo, Sharika
South Africa, Tygerberg
South African Medical Research Council
Moodley, Jothi
South Africa, Tygerberg
South African Medical Research Council
Premrajh, Anamika
South Africa, Tygerberg
South African Medical Research Council
Zako, Linda M.G.
South Africa, Tygerberg
South African Medical Research Council
Grosskurth, Heiner
Uganda, Entebbe
Uganda Virus Research Institute
Kamali, Anatoli
Uganda, Entebbe
Uganda Virus Research Institute
Kaleebu, Pontiano P.
Uganda, Entebbe
Uganda Virus Research Institute
Bahemuka, Ubaldo Mushabe
Uganda, Entebbe
Uganda Virus Research Institute
Mugisha, Joseph Okello
Uganda, Entebbe
Uganda Virus Research Institute
Miró, José María
Spain, Barcelona
Institut D'investigacions Biomèdiques August pi I Sunyer - Idibaps
Manzardo, Christian
Spain, Barcelona
Institut D'investigacions Biomèdiques August pi I Sunyer - Idibaps
Pumarola Suñé, Tomás
Spain, Barcelona
Institut D'investigacions Biomèdiques August pi I Sunyer - Idibaps
Gatell, José Mariá A.
Spain, Barcelona
Institut D'investigacions Biomèdiques August pi I Sunyer - Idibaps
Fisher, Martin J.
United Kingdom, Brighton
Royal Sussex County Hospital
Perry, Nicky
United Kingdom, Brighton
Royal Sussex County Hospital
Mulcahy, Fiona M.
Ireland, Dublin
St James's Hospital
Leen, Clifford L.S.
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Morris, Sheila
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Simmonds, Peter N.
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Gazzard, Brian G.
United Kingdom, London
Chelsea and Westminster Hospital
Higgs, Chris J.
United Kingdom, London
Chelsea and Westminster Hospital
Williams, Ian G.
United Kingdom, London
University College London
Pellegrino, Pierre
United Kingdom, London
University College London
Arenas-Pinto, Alejandro
United Kingdom, London
University College London
Ainsworth, Jonathan G.
United Kingdom, London
North Middlesex University Hospital
Johnson, Margaret A.
United Kingdom, London
The Royal Free Hospital
Kinloch, Sabine
United Kingdom, London
The Royal Free Hospital
Orkin, Chloë M.
United Kingdom, London
Barts Health Nhs Trust
Hand, James
United Kingdom, London
Barts Health Nhs Trust
de Souza, Carl B.S.S.
United Kingdom, London
Barts Health Nhs Trust
Thomson, Emma C.
United Kingdom, London
St Mary's Hospital
Fox, Julie Meriel
United Kingdom, London
St Mary's Hospital
Legg, Kenneth
United Kingdom, London
St Mary's Hospital
Winston, Alan
United Kingdom, London
St Mary's Hospital
Taylor, Stephen Charles
United Kingdom, Birmingham
Heartlands Hospital
Statistics
Citations: 32
Authors: 140
Affiliations: 36
Identifiers
Doi:
10.1098/rstb.2014.0241
ISSN:
09628436
Research Areas
Infectious Diseases