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Consequences of host heterogeneity, epitope immunodominance, and immune breadth for strain competition.

ABSTRACT: Consumer-resource dynamics of hosts with their pathogens are modulated by complex interactions between various branches of hosts' immune systems and the imperfectly perceived pathogen. Multistrain SIR models tend to sweep competitive interaction terms between different pathogen strains into a single parameter representing cross-immunity. After reviewing several hypotheses about the generation of immune responses, we look into the consequences of assuming that hosts with identical immune repertoires respond to new pathogens identically. In particular, we vary the breadth of the typical immune response, or the average number of pathogen epitopes a host perceives, and the probability of perceiving a particular epitope. The latter quantity in our model is equivalent both to the degree of diversity in host responses at the population level and the relative immunodominance of different epitopes. We find that a sharp transition to strain coexistence occurs as host responses become narrow or skewed toward one epitope. Increasing the breadth of the immune response and the immunogenicity of different epitopes typically increases the range of cross-immunity values in which chaotic strain dynamics and competitive exclusion occur. Models attempting to predict the outcomes of strain competition should thus consider the potential diversity and specificity of hosts' responses to infection.

SUBMITTER: Cobey S

PROVIDER: S-EPMC3042250 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Consequences of host heterogeneity, epitope immunodominance, and immune breadth for strain competition.

Cobey Sarah S Pascual Mercedes M

Journal of theoretical biology 20101118 1

Consumer-resource dynamics of hosts with their pathogens are modulated by complex interactions between various branches of hosts' immune systems and the imperfectly perceived pathogen. Multistrain SIR models tend to sweep competitive interaction terms between different pathogen strains into a single parameter representing cross-immunity. After reviewing several hypotheses about the generation of immune responses, we look into the consequences of assuming that hosts with identical immune repertoi ...[more]

PMID: 21093455

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Project description:It is becoming increasingly clear that many diseases are the result of infection from multiple genetically distinct strains of a pathogen. Such multi-strain infections have the capacity to alter both disease and pathogen dynamics. Infection with multiple strains of human cytomegalovirus (HCMV) is common and has been linked to enhanced disease. Suggestions that disease enhancement in multi-strain infected patients is due to complementation have been supported by trans-complementation studies in mice during co-infection of wild type and gene knockout strains of murine CMV (MCMV). Complementation between naturally circulating strains of CMV has, however, not been assessed. In addition, many models of multi-strain infection predict that co-infecting strains will compete with each other and that this competition may contribute to selective transmission of more virulent pathogen strains. To assess the outcome of multi-strain infection, C57BL/6 mice were infected with up to four naturally circulating strains of MCMV. In this study, profound within-host competition was observed between co-infecting strains of MCMV. This competition was MCMV strain specific and resulted in the complete exclusion of certain strains of MCMV from the salivary glands of multi-strain infected mice. Competition was dependent on Ly49H(+) natural killer (NK) cells as well as the expression of the ligand for Ly49H, the MCMV encoded product, m157. Strains of MCMV which expressed an m157 gene product capable of ligating Ly49H were outcompeted by strains of MCMV expressing variant m157 genes. Importantly, within-host competition prevented the shedding of the less virulent strains of MCMV, those recognized by Ly49H, into the saliva of multi-strain infected mice. These data demonstrate that NK cells have the strain specific recognition capacity required to meditate within-host competition between strains of MCMV. Furthermore, this within-host competition has the capacity to shape the dynamics of viral shedding and potentially select for the transmission of more virulent virus strains.

Dataset Information

Consequences of host heterogeneity, epitope immunodominance, and immune breadth for strain competition.

Publications

Consequences of host heterogeneity, epitope immunodominance, and immune breadth for strain competition.

Similar Datasets

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