Christopher M. Robinson1, Xiaohong Zhou1, Jaya Rajaiya1, M. Yousuf1, Gurdeep Singh1, Joshua J. DeSerres2, Michael P. Walsh3, Sallene Wong2, Donald Seto3, David W. Dyer4, James Chodosh1, Morris S. Jones3
1Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
2Provincial Laboratory for Public Health, Calgary, Alberta, Canada
3School of Systems Biology, George Mason University, Manassas, Virginia, USA
4Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Tóm tắt
ABSTRACT
For DNA viruses, genetic recombination, addition, and deletion represent important evolutionary mechanisms. Since these genetic alterations can lead to new, possibly severe pathogens, we applied a systems biology approach to study the pathogenicity of a novel human adenovirus with a naturally occurring deletion of the canonical penton base Arg-Gly-Asp (RGD) loop, thought to be critical to cellular entry by adenoviruses. Bioinformatic analysis revealed a new highly recombinant species D human adenovirus (HAdV-D60). A synthesis of
in silico
and laboratory approaches revealed a potential ocular tropism for the new virus.
In vivo
, inflammation induced by the virus was dramatically greater than that by adenovirus type 37, a major eye pathogen, possibly due to a novel alternate ligand, Tyr-Gly-Asp (YGD), on the penton base protein. The combination of bioinformatics and laboratory simulation may have important applications in the prediction of tissue tropism for newly discovered and emerging viruses.
IMPORTANCE
The ongoing dance between a virus and its host distinctly shapes how the virus evolves. While human adenoviruses typically cause mild infections, recent reports have described newly characterized adenoviruses that cause severe, sometimes fatal human infections. Here, we report a systems biology approach to show how evolution has affected the disease potential of a recently identified novel human adenovirus. A comprehensive understanding of viral evolution and pathogenicity is essential to our capacity to foretell the potential impact on human disease for new and emerging viruses.
