The influence of host diversity, transmission and microbiome on virulence evolution

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Title The influence of host diversity, transmission and microbiome on virulence evolution
Publication Type dissertation
School or College College of Science
Department Biological Sciences
Author Cornwall, Douglas H.
Date 2017
Description The harm caused to a host (virulence) is an important aspect to any pathogenic infection and is influenced by many different factors. Here I seek to understand how three of these factors, host genetic diversity, transmission, and gut microbial diversity, influence the virulence of a murine specific retrovirus, Friend Virus Complex (FVC). Chapter 1 explores the effect of major histocompatibility complex (MHC) diversity on virulence. Using serial passage of FVC, through either MHC similar or MHC dissimilar mice, I show that there is a significant reduction of both fitness and virulence of FVC when a dissimilar genotype is seen than when FVC is passaged through the same genotype; suggesting that MHC diversity is an impediment to virulence evolution. Furthermore, the alternating patterns reemerged after infection with a virus adapted to resistant animals that initially swamped the alternating effect, providing evidence for negative frequency-dependent selection maintaining MHC diversity in host populations. Chapter 2 elucidates the influences natural transmission, sex, and social status have on virulence using wild-derived contact (initially uninfected) and index (initially infected) animals in seminatural enclosures. Male-male transmission is the predominant mode of transmission as minimal female transmission and no vertical transmission was observed. Moreover, natural transmission is an impediment to FVC replication as infected contact animals had lower viral titer and virulence than index animals. Finally, though dominant and nondominant males contract the virus at similar rates and experience similar virulence, nondominant animals have higher titers. Chapter 3 seeks to understand how the microbiome influences pathogen virulence. After antibiotic treatment, animals of two different MHC congenic genotypes were reconstituted with gut microbiota from a donor of their own MHC genotype (native) or from a donor with a different MHC genotype (novel). After challenge with FVC, significantly higher titers were seen in animals receiving novel microbiota than animals receiving native microbiomes. There was only a shift down in total T-lymphocyte number in novel groups as no other cell subsets tested showed a change in abundance. The work presented here allows us to gain a better understanding of how virulence is impacted by a multitude of different forces, and that many different aspects need to be taken into account when trying to determine the evolution of virulence.
Type Text
Publisher University of Utah
Subject Evolutionary Biology; Friend Virus Complex; Major Histocompatibility Compex; Microbiome; Natural transmission
Dissertation Name Doctor of Philosophy
Language eng
Rights Management ©Douglas H. Cornwall
Format application/pdf
Format Medium application/pdf
ARK ark:/87278/s6hm9f1m
Setname ir_etd
ID 1349729
Reference URL https://collections.lib.utah.edu/ark:/87278/s6hm9f1m
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