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Cell tropism predicts long-term nucleotide substitution rates of mammalian RNA viruses
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Hicks, Allison. Cell tropism predicts long-term nucleotide substitution rates of mammalian RNA viruses. Retrieved from https://doi.org/doi:10.7282/T3K35RPC

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TitleCell tropism predicts long-term nucleotide substitution rates of mammalian RNA viruses
NameHicks, Allison (author); Duffy, Siobain (chair); Hillman, Bradley (internal member); Kahn, Peter C. (internal member); Rutgers University; Graduate School - New Brunswick
Date Created2013
Other Date2013-10 (degree)
SubjectMicrobial Biology, RNA viruses, Nucleotides, Mammals--Cytology
Extentvii, 62 p. : ill.
DescriptionThe high rates of RNA virus evolution are generally attributed to replication with error-prone RNA-dependent RNA polymerases. However, these long-term nucleotide substitution rates span three orders of magnitude and do not correlate well with mutation rates or selection pressures. This substitution rate variation may be explained by differences in virus ecology or intrinsic genomic properties. We generated long-term nucleotide substitution rate estimates for mammalian RNA viruses and compiled comparable published rates, yielding a dataset of 118 substitution rates of structural genes from 51 different species, as well as 40 rates of non-structural genes from 28 species. Through multiple regression analyses, we evaluated the relationships between these rates and four ecological factors: target cell, transmission route, host range, infection duration; and three genomic properties: genome length, genome sense, genome segmentation. Of these seven factors, we found target cells to be the only significant predictors of viral substitution rates, with tropisms for epithelial cells (P<2x10-5 for the structural genes) or neurons (P<3x10-7 and P<0.01 for the structural genes and non-structural genes, respectively) as the most significant predictors. Further, one-tailed t-tests showed that viruses primarily infecting epithelial cells evolve significantly faster than neurotropic viruses (P=1.83x10-10 and P=6.30x10-4 for the structural genes and non-structural genes, respectively). These results provide strong evidence that the fastest evolving mammalian RNA viruses infect cells with the highest turnover rates: the highly proliferative epithelial cells. Estimated viral generation times suggest that epithelial-infecting viruses replicate more quickly than viruses with different cell tropisms. Our results indicate that cell tropism is a key factor in viral evolvability.
NoteM.S.
NoteIncludes bibliographical references
Noteby Allison Hicks
Genretheses, ETD graduate
Persistent URLhttps://doi.org/doi:10.7282/T3K35RPC
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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