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Singh, Gurdeep

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Singh, Gurdeep

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20132

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Author's Publications: search.filters.isAuthorOfPublication.44743b98-2a2f-47d3-bf8a-49ac8212ea94

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    Predicting the Next Eye Pathogen: Analysis of a Novel Adenovirus
    (American Society of Microbiology, 2013) Robinson, Christopher; Zhou, Xiaohong; Rajaiya, Jaya; Yousuf, Mohammad Abu; Singh, Gurdeep; DeSerres, Joshua J.; Walsh, Michael P.; Wong, Sallene; Seto, Donald; Dyer, David W.; Chodosh, James; Jones, Morris S.
    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.
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    Molecular evolution of human adenoviruses
    (Nature Publishing Group, 2013) Robinson, Christopher; Singh, Gurdeep; Lee, Jeong Yoon; Dehghan, Shoaleh; Rajaiya, Jaya; Liu, Elizabeth B.; Yousuf, Mohammad Abu; Betensky, Rebecca; Jones, Morris S.; Dyer, David W.; Seto, Donald; Chodosh, James
    The recent emergence of highly virulent human adenoviruses (HAdVs) with new tissue tropisms underscores the need to determine their ontogeny. Here we report complete high quality genome sequences and analyses for all the previously unsequenced HAdV serotypes (n = 20) within HAdV species D. Analysis of nucleotide sequence variability for these in conjunction with another 40 HAdV prototypes, comprising all seven HAdV species, confirmed the uniquely hypervariable regions within species. The mutation rate among HAdV-Ds was low when compared to other HAdV species. Homologous recombination was identified in at least two of five examined hypervariable regions for every virus, suggesting the evolution of HAdV-Ds has been highly dependent on homologous recombination. Patterns of alternating GC and AT rich motifs correlated well with hypervariable region recombination sites across the HAdV-D genomes, suggesting foci of DNA instability lead to formulaic patterns of homologous recombination and confer agility to adenovirus evolution.