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.

Genome Sequence of the First Human Adenovirus Type 14 Isolated in China

“…Fifty-one years later, a re-emerging variant, HAdV-14p1, was associated with several highly contagious outbreaks of acute respiratory disease (ARD), including fatalities, in the United States (2006 to 2009) (2, 4, 7) and Europe (2009 and 2010) (1). Additionally, as one of the two parental viruses contributing to the genome of an emergent ARD pathogen, HAdV-B55 (14,16), it is valuable to have the genomes of current circulating strains available for study in order to determine if there is a propensity for HAdV-B14 and HAdV-B11 to recombine, creating a "Trojan horse" in which the presenting antibody epitope is of a renal pathogen and the virus chassis and clinical presentation are of a respiratory pathogen (12). The isolation of HAdV-B14 in China is intriguing, as three recent HAdV-B55 outbreaks were in China in 2006 (14,16) .…”

“…Additionally, as one of the two parental viruses contributing to the genome of an emergent ARD pathogen, HAdV-B55 (14,16), it is valuable to have the genomes of current circulating strains available for study in order to determine if there is a propensity for HAdV-B14 and HAdV-B11 to recombine, creating a "Trojan horse" in which the presenting antibody epitope is of a renal pathogen and the virus chassis and clinical presentation are of a respiratory pathogen (12). The isolation of HAdV-B14 in China is intriguing, as three recent HAdV-B55 outbreaks were in China in 2006 (14,16) . This is unusual in that the symptoms were not as previously described for published HAdV-B14 and HAdV-B55 infections (1, 2, 3, 7, 14, 16).…”

Genome Sequence of Human Adenovirus Type 55, a Re-Emergent Acute Respiratory Disease Pathogen in China

“…Among these, HAdV-B55 is either (i) a very uncommon re-emergent pathogen, first identified as HAdV-B11a from an outbreak during a military training exercise (Spain, 1969), albeit by partial characterization of its hexon and fiber epitopes (3), and with a second appearance in another military training exercise (Turkey, 2004) (1), or (ii) a newly identified emergent acute respiratory disease (ARD) pathogen, fully characterized by whole-genome sequencing, causing two recent outbreaks, one in China in 2006 (15) and one in Singapore in 2005 (4). In 2011, 5 years after the first HAdV-B55-associated ARD outbreak in China (Qishan County, Shanxi Province), this pathogen apparently re-emerged in Beijing, causing several cases of ARD; one sample was obtained from a 29-yearold patient diagnosed with severe community-acquired pneumonia (2).…”

Five Genome Sequences of Subspecies B1 Human Adenoviruses Associated with Acute Respiratory Disease

“…Minimally, the sequence coverages were at 8-fold (Sanger chemistry) and 17-to 20-fold (Next Gen), with the Next Gen data noted by Operon at an accuracy of greater than 99% (Q20 or better). Recombination plays a major role in generating HAdV genetic diversity (3,(9)(10)(11)(12)(13). This has been thoroughly demonstrated by the recent sequencing and bioinformatic analysis of the genomes of newly emergent and prevalent pathogenic strains (3,(9)(10)(11)(12)(13).…”

“…Recombination plays a major role in generating HAdV genetic diversity (3,(9)(10)(11)(12)(13). This has been thoroughly demonstrated by the recent sequencing and bioinformatic analysis of the genomes of newly emergent and prevalent pathogenic strains (3,(9)(10)(11)(12)(13). Insights from detailed analysis of a diversity of genomes and their in silico proteomes will facilitate the design of experimental strategies to understand the correlation of specific genome attributes with pathogenic phenotypes.…”