Genomic analyses of recombinant adenovirus type 11a in China

Abstract

Whole-genome sequencing of human adenovirus type 11 (HAdV-11) strain QS, isolated in China, was conducted, and its sequence was compared with the sequences of strains within the species of HAdVs. The HAdV-11 QS genome contains 34,755 nucleotides. Similar to the other HAdV subgenus B sequences, the HAdV-11 QS genome coded 37 functional proteins and could be divided into four early, two intermediate, and five late transcription regions. The amino acid sequences of the fiber and the hypervariable regions (HVRs) within the hexon gene of HAdV-11 QS were identical to the corresponding sequences of the HAdV-11a strain; further analyses that compared those amino acid sequences with the amino acid sequences of the HAdV species subgenus B:2 strains revealed that the highest degree of homology (>99.2%) existed between HAdV-11 QS and the prototypical HAdV-14 strain, except for a few coding sequences of HVRs within the hexon gene, DNA polymerase, pVI, and pre-terminal protein. This indicate that HAdV-11 strain QS, isolated in China, is a recombinant adenovirus of HAdV-14, and the recombination analyses also confirmed this finding. It is difficult to clarify the time and manner of the recombination, and further investigations are required to determine whether the emergence of recombination between HAdV-11a and HAdV-14 might increase virulence, thereby posing a new global challenge with regard to acute respiratory diseases in the near future.

FIG. 1.

(A) Phylogenetic analyses of a few main functional genes of HAdV-11 strain QS (L4-100K, DBP, DNA polymerase, fiber, hexon, penton, pIIIa, pVI, pTP, and pVII). The corresponding subgenus types are indicated within parentheses after the respective serotypes. The GenBank accession numbers of the available fiber of HAdV-11a is L08232. (B) Phylogenetic analysis of the whole-genome sequence of HAdV. The GenBank accession numbers of the following serotypes are given in parentheses: HAdV-3 (AY599834), HAdV-4 (AY594253), HAdV-5 (AY601635), HAdV-7 (AY594255), HAdV-11 (AF532578), HAdV-12 (AC_000005), HAdV-14 (AY803294), HAdV-16 (AY601636), HAdV-21 (AY601633), HAdV-26 (EF153474), HAdV-34 (AY737797), HAdV-35 (AY128640), HAdV-40 (NC_001454), HAdV-50 (AY737798), HAdV-52 (DQ923122), and SAd-21(AC_000010). A, HAdV-A; B:1, HAdV-B1; B:2, HAdV-B2; C, HAdV-C; D, HAdV-D; E, HAdV-E; F, HAdV-F; G, HAdV-G. The relative phylogenetic distances were measured from the lowest scales of each phylogenetic tree (0.05).

FIG. 2.

Similarities in the whole genome of HAdV strain QS compared to the sequences of the prototypical B:2 species strains of HAdV (HAdV-11p, HAdV-14, HAdV-34, and HAdV-35). The upper graph shows the results of similarity analysis, while the lower graph shows the results of bootscan analysis. The window is 400 bp, and the step is 20 bp. The Kimura model with the Jukes-Cantor correction was used. The vertical axis indicates the percentage of nucleotide similarity and the permuted trees between HAdV QS and the four strains representing the four serotypes of HAdV-B2. The horizontal axis indicates the nucleotide positions in the whole genome.