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Philos Trans R Soc Lond B Biol Sci. 2015 Sep 5;370(1676). pii: 20140241. doi: 10.1098/rstb.2014.0241.

Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals.

Collaborators (173)

Breckenridg A, Clayden P, Conlon C, Conradie F, Kaldor J, Maggiolo F, Ssali F, Cooper D, Kaleebu P, Ramjee G, Schechter M, Tambussi G, Weber J, Fidler S, Babiker A, Peto T, McLaren A, Beral V, Chene G, Hakim J, Babiker A, Porter K, Thomason M, Ewings F, Gabriel M, Johnson D, Thompson K, Cursley A, Donegan K, Fossey E, Kelleher P, Lee K, Murphy B, Nock D, Phillips R, Frater J, Laursen L, Robinson N, Goulder P, Brown H, McClure M, Bonsall D, Erlwein O, Helander A, Kaye S, Robinson M, Cook L, Adcock G, Ahmed P, Paton N, Fidler S, Kelleher A, Moore R, McFarlane R, Roth N, Finlayson R, Tee B, Read T, Kelly M, Grey P, Cooper D, Kelleher A, Law M, Schechter M, Gama P, Mercon M, de Souza M, Yoshida C, Silva J, Amaral A, de Aguiar D, de Fatima Melo M, Garrido R, Tambussi G, Nozza S, Pogliaghi M, Chiappetta S, Torre L, Gasparotto E, D'Offizi G, Vlassi C, Corpolongo A, Wood R, Pitt J, Orrell C, Cilliers F, Croxford R, Middelkoop K, Bekker L, Heiberg C, Aploon J, Killa N, Fielder E, Buhler T, Rees H, Venter F, Palanee T, Stevens W, Ingram C, Majam M, Papathanasopoulos M, Ramjee G, Gappoo S, Moodley J, Premrajh A, Zako L, Grosskurth H, Kamali A, Kaleebu P, Bahemuka U, Mugisha J, Njaj H, Miro J, Lopez-Dieguez M, Manzardo C, Arnaiz J, Pumarola T, Plana M, Tuset M, Ligero M, Garcıa M, Gallart T, Gatell J, Fisher M, Hobbs K, Perry N, Pao D, Maitland D, Heald L, Mulcahy F, Courtney G, Reidy D, Leen C, Scott G, Ellis L, Morris S, Simmonds P, Gazzard B, Hawkins D, Higgs C, Anderson J, Mguni S, Williams I, De Esteban N, Pellegrino P, Arenas-Pinto A, Cornforth D, Turner J, Ainsworth J, Waters A, Johnson M, Kinloch S, Carroll A, Byrne P, Cuthbertson Z, Orkin C, Hand J, De Souza C, Weber J, Fidler S, Hamlyn E, Thomson E, Fox J, Legg K, Mullaney S, Winston A, Wilson S, Ambrose P, Taylor S, Gilleran G, Keeling S, Becker A, Boocock C.

Author information

1
Department of Zoology, University of Oxford, Oxford, UK.
2
Wellcome Trust Sanger Institute, Cambridge, UK.
3
Wellcome Trust Sanger Institute, Cambridge, UK Cambridge Institute of Medical Research, University of Cambridge, Cambridge, UK.
4
Faculty of Medicine, Imperial College, London, UK.
5
Wellcome Trust Sanger Institute, Cambridge, UK MRC/UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, UK.
6
Department of Zoology, University of Oxford, Oxford, UK oliver.pybus@zoo.ox.ac.uk.

Abstract

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 anti-retroviral 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 anti-retroviral 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 HIV-infected 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, and we 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.

KEYWORDS:

B-cell receptor; Gini index; diversity

PMID:
26194755
PMCID:
PMC4528418
DOI:
10.1098/rstb.2014.0241
[Indexed for MEDLINE]
Free PMC Article

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