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Pervasive and non-random recombination in near full-length HIV genomes from Uganda

Research output: Contribution to journalArticle

  • Heather Grant
  • Emma Hodcroft
  • Deogratius Ssemwanga
  • Luis Roger Esquivel Gomez
  • Dan Frampton
  • Astrid Gall
  • Paul Kellam
  • Tulio de Oliveira
  • Rebecca N Nsubuga
  • Freddie Kibengo
  • Tsz Ho Kwan
  • David Robertson
  • Oliver Ratmann
  • Christophe Fraser
  • Deenan Pillay
  • Pontiano Kaleebu

Related Edinburgh Organisations

Original languageEnglish
JournalVirus Evolution
Publication statusAccepted/In press - 2 Jan 2020

Abstract

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 1472 consensus genome sequences over 5kb have been obtained from 1857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6%) of which were near-full length sequences (>8kb). Using the subtyping tool SCUEAL we find that of the near-full length dataset, 233 (50.1%) genomes contained only one subtype, 30.8% A1 (n=143), 17.6% D (n=82) and 1.7% C (n=8), while 49.9%(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 CRF was found, there was limited evidence of the transmission of breakpoints, and the vast majority (153/164; 93%) of the A1/D recombinants appear to be unique recombinant forms (URFs). Thus, recombination is pervasive with clear biases in breakpoint location, but circulating recombinant forms (CRFs) are not a significant feature, characteristic of a complex and diverse epidemic.

    Research areas

  • HIV, Genome, subtypes, phylogenetics, recombination, breakpoints

ID: 130131929