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Host exposure history modulates the within-host advantage of virulence in a songbird-bacterium system.

ABSTRACT: The host immune response can exert strong selective pressure on pathogen virulence, particularly when host protection against reinfection is incomplete. Since emerging in house finch populations, the bacterial pathogen Mycoplasma gallisepticum (MG) has been increasing in virulence. Repeated exposure to low-doses of MG, a proxy for what birds likely experience while foraging, provides significant but incomplete protection against reinfection. Here we sought to determine if the within-host, pathogen load advantage of high virulence is mediated by the degree of prior pathogen exposure, and thus the extent of immune memory. We created variation in host immunity by experimentally inoculating wild-caught, MG-naïve house finches with varying doses and number of exposures of a single pathogen strain of intermediate virulence. Following recovery from priming exposures, individuals were challenged with one of three MG strains of distinct virulence. We found that the quantitative pathogen load advantage of high virulence was strongly mediated by the degree of prior exposure. The greatest within-host load advantage of virulence was seen in hosts given low-dose priming exposures, akin to what many house finches likely experience while foraging. Our results show that incomplete host immunity produced by low-level prior exposure can create a within-host environment that favors more virulent pathogens.

SUBMITTER: Leon AE

PROVIDER: S-EPMC6937340 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Host exposure history modulates the within-host advantage of virulence in a songbird-bacterium system.

Leon Ariel E AE Fleming-Davies Arietta E AE Hawley Dana M DM

Scientific reports 20191230 1

The host immune response can exert strong selective pressure on pathogen virulence, particularly when host protection against reinfection is incomplete. Since emerging in house finch populations, the bacterial pathogen Mycoplasma gallisepticum (MG) has been increasing in virulence. Repeated exposure to low-doses of MG, a proxy for what birds likely experience while foraging, provides significant but incomplete protection against reinfection. Here we sought to determine if the within-host, pathog ...[more]

PMID: 31889059

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Project description:Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus.

Dataset Information

Host exposure history modulates the within-host advantage of virulence in a songbird-bacterium system.

Publications

Host exposure history modulates the within-host advantage of virulence in a songbird-bacterium system.

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