Genotypes and phylogenetic analysis of adenovirus in children with respiratory infection in Buenos Aires, Argentina (2000-2018)

Abstract

Human adenoviruses (HAdV) are one of the most frequent causes of respiratory infections around the world, causing mild to severe disease. In Argentina, many studies focused on the association of HAdV respiratory infection with severe disease and fatal outcomes leading to the discovery in 1984 of a genomic variant 7h associated with high fatality. Although several molecular studies reported the presence of at least 4 HAdV species (B, C, D and E) in Argentina, few sequences were available in the databases. In this study, sequences from the hexon gene region were obtained from 141 patients as a first approach to assess the genetic diversity of HAdVs circulating in Buenos Aires, Argentina. Phylogenetic analysis of these sequences and others recovered from public databases confirmed the circulation of the four above-mentioned species represented by 11 genotypes, with predominance in species B and C and shifts in their proportion in the studied period (2000 to 2018). The variants detected in Argentina, for most of the genotypes, were similar to those already described in other countries. However, uncommon lineages belonging to genotypes C2, C5 and E4 were detected, which might indicate the circulation of local variants and will deserve further studies of whole-genome sequences.

Fig 1. Phylogenetic tree of HAdV strains from children with acute respiratory infection in Buenos Aires, Argentina -2000 to 2018.

Buenos Aires samples are in red, named by the laboratory identification number followed by the isolation year. GenBank accession numbers of all available reference sequences (blue) are shown. Phylogenetic trees obtained by Maximum Likelihood methodology based on the HAdV partial hexon gene (HVR 1–6) by HAdV species. For each dataset the best fit model was used: I. TPMuf+Γ, II. TIM2+ Γ+I, III. TIM2+ Γ+I. The branch support was determined by bootstrapping (1000 pseudoreplica).

Fig 2. Phylogenetic analyses of HAdV genotypes C2 (I), C5 (II) and E4 (III).

Maximum likelihood phylogenetic trees for sequences from Argentina (red), and from other countries (black). The number between square brackets indicates how many additional HAdV sequences had the same position in the complete tree. The reference sequence(s) for each genotype are in blue. The best fit model was used according to Bayesian Information Criterion (I: HKY+I, II and III: HKY+Γ) for each tree. The numbers near the node represent the branch support (bootstrap % over 1000 pseudoreplica). Amino acid signature or particular features are described at the right of each cluster. I. AR Clade: sequences with an amino acid substitution E to K in the duplicated codon. III. Hollow bullets: sequence with a 4 amino acid deletion at positions 192 to 195.

Fig 3. Sequence differences between HAdV-C2 clusters.

Differences at the sequenced region for HAdV C2, C89 and AR Clade are shown. For each position, the upper letters represent one-letter amino acid codes, and below the nucleotide triplet that encodes it. Letters in bold representing non-synonymous substitutions, also shown as dotted lines in the genome. Letters with light blue background represent synonymous substitutions. Type: Syn for synonymous and NoSys for non-synonymous substitutions. Question marks indicate sites that are singletons in AR Clade but are shared with C2.