Evidence of molecular evolution driven by recombination events influencing tropism in a novel human adenovirus that causes epidemic keratoconjunctivitis

Michael P. Walsh, Ashish Chintakuntlawar, Christopher M. Robinson, Ijad Madisch, Balázs Harrach, Nolan R. Hudson, David Schnurr, Albert Heim, James Chodosh, Donald Seto, Morris S. Jones

Research output: Contribution to journalArticle

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Abstract

In 2005, a human adenovirus strain (formerly known as HAdV-D22/H8 but renamed here HAdV-D53) was isolated from an outbreak of epidemic keratoconjunctititis (EKC), a disease that is usually caused by HAdV-D8, -D19, or -D37, not HAdV-D22. To date, a complete change of tropism compared to the prototype has never been observed, although apparent recombinant strains of other viruses from species Human adenovirus D (HAdV-D) have been described. The complete genome of HAdV-D53 was sequenced to elucidate recombination events that lead to the emergence of a viable and highly virulent virus with a modified tropism. Bioinformatic and phylogenetic analyses of this genome demonstrate that this adenovirus is a recombinant of HAdV-D8 (including the fiber gene encoding the primary cellular receptor binding site), HAdV-D22, (the ε determinant of the hexon gene), HAdV-D37 (including the penton base gene encoding the secondary cellular receptor binding site), and at least one unknown or unsequenced HAdV-D strain. Bootscanning analysis of the complete genomic sequence of this novel adenovirus, which we have re-named HAdV-D53, indicated at least five recombination events between the aforementioned adenoviruses. Intrahexon recombination sites perfectly framed the ε neutralization determinant that was almost identical to the HAdV-D22 prototype. Additional bootscan analysis of all HAdV-D hexon genes revealed recombinations in identical locations in several other adenoviruses. In addition, HAdV-D53 but not HAdV-D22 induced corneal inflammation in a mouse model. Serological analysis confirmed previous results and demonstrated that HAdV-D53 has a neutralization profile representative of the ε determinant of its hexon (HAdV-D22) and the fiber (HAdV-D8) proteins. Our recombinant hexon sequence is almost identical to the hexon sequences of the HAdV-D strain causing EKC outbreaks in Japan, suggesting that HAdV-D53 is pandemic as an emerging EKC agent. This documents the first genomic, bioinformatic, and biological descriptions of the molecular evolution events engendering an emerging pathogenic adenovirus.

Original languageEnglish (US)
Article numbere5635
JournalPloS one
Volume4
Issue number6
DOIs
StatePublished - Jun 3 2009
Externally publishedYes

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Keratoconjunctivitis
Human Adenoviruses
keratoconjunctivitis
tropisms
Tropism
Human adenovirus D
Molecular Evolution
Adenoviridae
Genetic Recombination
Genes
Gene encoding
Bioinformatics
Viruses
Computational Biology
Binding Sites
Disease Outbreaks
bioinformatics
prototypes
neutralization
Fibers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Evidence of molecular evolution driven by recombination events influencing tropism in a novel human adenovirus that causes epidemic keratoconjunctivitis. / Walsh, Michael P.; Chintakuntlawar, Ashish; Robinson, Christopher M.; Madisch, Ijad; Harrach, Balázs; Hudson, Nolan R.; Schnurr, David; Heim, Albert; Chodosh, James; Seto, Donald; Jones, Morris S.

In: PloS one, Vol. 4, No. 6, e5635, 03.06.2009.

Research output: Contribution to journalArticle

Walsh, Michael P. ; Chintakuntlawar, Ashish ; Robinson, Christopher M. ; Madisch, Ijad ; Harrach, Balázs ; Hudson, Nolan R. ; Schnurr, David ; Heim, Albert ; Chodosh, James ; Seto, Donald ; Jones, Morris S. / Evidence of molecular evolution driven by recombination events influencing tropism in a novel human adenovirus that causes epidemic keratoconjunctivitis. In: PloS one. 2009 ; Vol. 4, No. 6.
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abstract = "In 2005, a human adenovirus strain (formerly known as HAdV-D22/H8 but renamed here HAdV-D53) was isolated from an outbreak of epidemic keratoconjunctititis (EKC), a disease that is usually caused by HAdV-D8, -D19, or -D37, not HAdV-D22. To date, a complete change of tropism compared to the prototype has never been observed, although apparent recombinant strains of other viruses from species Human adenovirus D (HAdV-D) have been described. The complete genome of HAdV-D53 was sequenced to elucidate recombination events that lead to the emergence of a viable and highly virulent virus with a modified tropism. Bioinformatic and phylogenetic analyses of this genome demonstrate that this adenovirus is a recombinant of HAdV-D8 (including the fiber gene encoding the primary cellular receptor binding site), HAdV-D22, (the ε determinant of the hexon gene), HAdV-D37 (including the penton base gene encoding the secondary cellular receptor binding site), and at least one unknown or unsequenced HAdV-D strain. Bootscanning analysis of the complete genomic sequence of this novel adenovirus, which we have re-named HAdV-D53, indicated at least five recombination events between the aforementioned adenoviruses. Intrahexon recombination sites perfectly framed the ε neutralization determinant that was almost identical to the HAdV-D22 prototype. Additional bootscan analysis of all HAdV-D hexon genes revealed recombinations in identical locations in several other adenoviruses. In addition, HAdV-D53 but not HAdV-D22 induced corneal inflammation in a mouse model. Serological analysis confirmed previous results and demonstrated that HAdV-D53 has a neutralization profile representative of the ε determinant of its hexon (HAdV-D22) and the fiber (HAdV-D8) proteins. Our recombinant hexon sequence is almost identical to the hexon sequences of the HAdV-D strain causing EKC outbreaks in Japan, suggesting that HAdV-D53 is pandemic as an emerging EKC agent. This documents the first genomic, bioinformatic, and biological descriptions of the molecular evolution events engendering an emerging pathogenic adenovirus.",
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