Pervasive and non-random recombination in near-full length HIV genomes from Uganda. HIV genomes assembled from clinical samples. Please see www.pangea-hiv.org for details and additional information.. Pervasive and non-random recombination in near-full length HIV genomes from Uganda

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 (both inter-and intra-subtype), and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium 1472 consensus genome sequences over 5 kb 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 (NFL) sequences (>8kb). Using the subtyping tool SCUEAL we find that of the NFL 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). Almost all of the genomes (91.8%) contained at least one detectable breakpoint, either intra- or inter-subtype. The frequency of recombination breakpoints along the genome is presented, and is found to be similar in intra-and inter-subtype recombinant genomes.Furthermore,K-means clustering of the recombinant A1/D genomes revealed a section of envelope (C2 gp120-TM gp41) 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, there was limited evidence of the transmission of breakpoints, and the vast majority (153/164; 93%) of the A1/D recombinants are unique recombinant forms (URFs).Thus, recombination is pervasive within and between subtypes with clear biases in breakpoint location, but circulating recombinant forms (CRFs) are not a significant feature, characteristic of a complex and diverse epidemic.