Insights of the genetic diversity of DENV-1 detected in Brazil in 25 years: Analysis of the envelope domain III allows lineages characterization.

Dengue virus type 1 (DENV-1) was first isolated in Brazil in 1986 in the state of Rio de Janeiro (RJ) and during 25years, this serotype emerged and re-emerged causing explosive epidemics in the country. Here, we aimed to present the phylogeny and molecular characterization based on the envelope gene (E) of DENV-1 (n=48) isolated during epidemics occurred from 1986 to 2011. Six full coding region genomes of DENV-1 were fully sequenced and possible genomic recombination events were analyzed. The results showed that the Brazilian DENV-1 isolates analyzed belong to genotype V (Americas/Africa), but grouping into distinct clades. Three groups were identified, one dating from 1986 to 2002 (lineage 1a), a second group isolated from 2009 to 2011 and a representative strain isolated in 2002 (lineage 2), and a group of strains isolated from 2010 to 2011 (lineage 1b). The lineages 1a and 1b were more closely related to the American strains, while lineage 2 to the Asian strains. Amino acids (aa) substitutions were observed in the domains I and III of the E protein and were associated to the lineages segregation. A substitution on E297 differentiated the lineage 1a from the lineages 1b and 2. Substitutions on E338, E394 (domain III), E428 and E436 (stem region) differentiated lineages 1a, 1b and 2. With the exception of the C gene, all the others genes analyzed allowed the DENV-1 classification into the distinct genotypes. Interestingly, the E gene's domain III and stem regions alone were able to characterize the distinct lineages, as observed by the analysis of the entire E gene and the complete coding region. No recombinant events were detected, but a strain belonging to lineage 1a was closely related to a known recombinant strain (AF513110/BR/2001).