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Pervasive and non-random recombination in near full-length HIV genomes from Uganda.
Grant, Heather E; Hodcroft, Emma B; Ssemwanga, Deogratius; Kitayimbwa, John M; Yebra, Gonzalo; Esquivel Gomez, Luis Roger; Frampton, Dan; Gall, Astrid; Kellam, Paul; de Oliveira, Tulio; Bbosa, Nicholas; Nsubuga, Rebecca N; Kibengo, Freddie; Kwan, Tsz Ho; Lycett, Samantha; Kao, Rowland; Robertson, David L; Ratmann, Oliver; Fraser, Christophe; Pillay, Deenan; Kaleebu, Pontiano; Leigh Brown, Andrew J.
Afiliação
  • Grant HE; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK.
  • Hodcroft EB; Biozentrum, University of Basel, Basel, Switzerland.
  • Ssemwanga D; Swiss Institute of Bioinformatics, Basel, Switzerland.
  • Kitayimbwa JM; Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda.
  • Yebra G; Uganda Virus Research Institute, Entebbe, Uganda.
  • Esquivel Gomez LR; Department of Mathematics, Makerere University, Kampala, Uganda.
  • Frampton D; The Roslin Institute, University of Edinburgh, Edinburgh, UK.
  • Gall A; Max Planck Institute for the Science of Human History, Jena, Germany.
  • Kellam P; Division of Infection and Immunity, University College London, London, UK.
  • de Oliveira T; European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK.
  • Bbosa N; European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK.
  • Nsubuga RN; Nelson R. Mandela School of Medicine, Africa Health Research Institute, Durban, South Africa.
  • Kibengo F; Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda.
  • Kwan TH; Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda.
  • Lycett S; Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda.
  • Kao R; Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Robertson DL; The Roslin Institute, University of Edinburgh, Edinburgh, UK.
  • Ratmann O; The Roslin Institute, University of Edinburgh, Edinburgh, UK.
  • Fraser C; MRC Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Pillay D; Department of Mathematics, Imperial College London, London, UK.
  • Kaleebu P; Nuffield Department of Medicine, Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
  • Leigh Brown AJ; European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK.
Virus Evol ; 6(1): veaa004, 2020 Jan.
Article em En | MEDLINE | ID: mdl-32395255
Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium, 1,472 consensus genome sequences over 5 kb have been obtained from 1,857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6 per cent) of which were near full-length sequences (>8 kb). Using the subtyping tool SCUEAL, we find that of the near full-length dataset, 233 (50.1 per cent) genomes contained only one subtype, 30.8 per cent A1 (n = 143), 17.6 per cent D (n = 82), and 1.7 per cent C (n = 8), while 49.9 per cent (n = 232) contained more than one subtype (including A1/D (n = 164), A1/C (n = 13), C/D (n = 9); A1/C/D (n = 13), and 33 complex types). K-means clustering of the recombinant A1/D genomes revealed a section of envelope (C2gp120-TMgp41) is often inherited intact, whilst a generalized linear model was used to demonstrate significantly fewer breakpoints in the gag-pol and envelope C2-TM regions compared with accessory gene regions. Despite similar recombination patterns in many recombinants, no clearly supported circulating recombinant form (CRF) was found, there was limited evidence of the transmission of breakpoints, and the vast majority (153/164; 93 per cent) of the A1/D recombinants appear to be unique recombinant forms. Thus, recombination is pervasive with clear biases in breakpoint location, but CRFs are not a significant feature, characteristic of a complex, and diverse epidemic.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Prognostic_studies Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Prognostic_studies Idioma: En Ano de publicação: 2020 Tipo de documento: Article