Journal article
Superinfection as a driver of genomic diversification in antigenically variant pathogens
Proceedings of the National Academy of Sciences - PNAS, Vol.105(6), pp.2123-2127
02/12/2008
Handle:
https://hdl.handle.net/2376/102005
PMCID: PMC2538888
PMID: 18252822
Abstract
A new pathogen strain can penetrate an immune host population only if it can escape immunity generated against the original strain. This model is best understood with influenza viruses, in which genetic drift creates antigenically distinct strains that can spread through host populations despite the presence of immunity against previous strains. Whether this selection model for new strains applies to complex pathogens responsible for endemic persistent infections, such as anaplasmosis, relapsing fever, and sleeping sickness, remains untested. These complex pathogens undergo rapid within-host antigenic variation by using sets of chromosomally encoded variants. Consequently, immunity is developed against a large repertoire of variants, dramatically changing the scope of genetic change needed for a new strain to evade existing immunity and establish coexisting infection, termed strain superinfection. Here, we show that the diversity in the alleles encoding antigenic variants between strains of a highly antigenically variant pathogen was equal to the diversity within strains, reflecting equivalent selection for variants to overcome immunity at the host population level as within an individual host. This diversity among strains resulted in expression of nonoverlapping variants that allowed a new strain to evade immunity and establish superinfection. Furthermore, we demonstrated that a single distinct allele allows strain superinfection. These results indicate that there is strong selective pressure to increase the diversity of the variant repertoire beyond what is needed for persistence within an individual host and provide an explanation, competition at the host population level, for the large genomic commitment to variant gene families in persistent pathogens.
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Details
- Title
- Superinfection as a driver of genomic diversification in antigenically variant pathogens
- Creators
- James E Futse - Programs in Vector-Borne Diseases and Genomics, College of Veterinary Medicine, Washington State University, Pullman, WA 99164; andKelly A Brayton - Programs in Vector-Borne Diseases and Genomics, College of Veterinary Medicine, Washington State University, Pullman, WA 99164; andMichael J Dark - Programs in Vector-Borne Diseases and Genomics, College of Veterinary Medicine, Washington State University, Pullman, WA 99164; andDonald P Knowles - Animal Diseases Research Unit, U.S. Department of Agriculture Agricultural Research Service, Pullman, WA 99164Guy H Palmer - Programs in Vector-Borne Diseases and Genomics, College of Veterinary Medicine, Washington State University, Pullman, WA 99164; and
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.105(6), pp.2123-2127
- Academic Unit
- Veterinary Microbiology and Pathology, Department of; Paul G. Allen School for Global Animal Health
- Publisher
- National Academy of Sciences
- Identifiers
- 99900546537401842
- Language
- English
- Resource Type
- Journal article