Origin and evolutionary history of HIV-1 subtype C in Brazil

Objective: To investigate the origin and to reconstruct the onset date of the HIV-1 subtype C epidemic in Brazil. Design: Three independent datasets of subtype C sequences isolated from HIV-1-positive patients from southern Brazil over a period of 15 years (1991-2006) were analyzed: 82 env V3 sequences (213nt), 40 env C2-C5 sequences (559nt), and 72 pol sequences (960nt). Methods: Brazilian sequences were compared with other subtype C reference strains from the database using basic local alignment search tool, phylogenetic analyses, and searching of specific amino acid signature patterns. Evolutionary parameters were estimated using a Bayesian coalescent-based method under either strict or relaxed molecular clock models. Results: HIV-1 subtype C sequences from Brazil and Burundi formed a monophyletic cluster at both env and pol regions and shared specific amino acid signatures in the protease region when compared with other viruses of the same subtype from around the world. All Brazilian strains arose as a monophyletic subcluster within the Burundi-Brazilian lineage, whereas isolates from Burundi appeared at the origin of the clade. Evolutionary analyses of both env and pol genomic regions indicate that the age of the most recent common ancestor of the Brazilian subtype C clade dates back to the early 1980s. Conclusion: The subtype C epidemic in the southern Brazilian region was initiated by the introduction of a single founder strain closely related to subtype C strains from Burundi. Our results suggest that this founder event probably took place around the early 1980s, roughly a decade before the previous estimates. (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.