Hot and Cold: Spatial Fluctuation in HIV-1 Recombination Rates

Coinfection of a single cell with two or more HIV strains may produce recombinant viruses upon template switching by the replication machinery. We applied a hierarchical multiple change point model to simultaneously infer inter-subtype recombination breakpoints and spatial variation in the recombination rate along the HIV-1 genome. We examined thousands of publicly available HIV-1 sequences representing the worldwide epidemic and focused on 544 unique recombinants with 1,701 recombination breakpoints. Estimates of per site recombination rate revealed the presence of a novel hotspot in the pol gene, surrounded by a cluster of mutations associated with resistance to reverse transcriptase inhibitors. We also confirm the presence of a known hotspot in the env gene and a previously hypothesized hotspot in the gag gene.