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Title: Expansion of variant diversity associated with high prevalence of pathogen strain superinfection under conditions of natural transmission

Author
item Ueti, Massaro
item TAN, YUNBING - Washington State University
item BROSCHAT, SHIRA LYNN - Washington State University
item CASTANEDA-ORTIZ, ELIZABETH - Autonomous National University Of Mexico
item CAMACHO-NUEZ, MINERVA - Autonomous National University Of Mexico
item MOSQUEDA, JUAN - University Of Mexico
item Scoles, Glen
item GRIMES, MATTHEW - Washington State University
item BRAYTON, KELLY - Washington State University
item PALMER, GUY - Washington State University

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/3/2012
Publication Date: 7/1/2012
Citation: Ueti, M.W., Tan, Y., Broschat, S., Castaneda-Ortiz, E., Camacho-Nuez, M., Mosqueda, J., Scoles, G.A., Grimes, M., Brayton, K., Palmer, G. 2012. Expansion of variant diversity associated with high prevalence of pathogen strain superinfection under conditions of natural transmission. Infection and Immunity. 80(7):2354-60.

Interpretive Summary: Superinfection occurs when a mammalian host that has already mounted an immune response to a primary strain becomes infected with a second genetically distinct pathogen strain. Successful superinfection would require that the secondary pathogen be antigenically different from the primary pathogen strain, and this occurs when the second strain expresses a unique set of antigenic variants. We tested the hypothesis that the superinfecting strain is antigenically different from the primary strain under natural transmission conditions in both temperate (United States) and tropical (Mexico) regions. In temperate regions single strain infections of Anaplasma marginale predominate, whereas superinfections predominate in tropical regions. Animals with naturally acquired superinfection had a statistically significantly greater number of unique variant sequences as compared to animals either experimentally or naturally infected with single strains. The greater number of unique sequences in superinfected hosts reflected a statistically significant increase in primary structural diversity. The increase in primary structural diversity reflected an increase in combinations of the newly identified hypervariable micro-domains. These observations support the conclusion that strain superinfection is associated with a significant increase in antigenic diversity.

Technical Abstract: Superinfection occurs when a second, genetically distinct strain infects a host that has already mounted an immune response to a primary strain. For antigenically variant pathogens, the primary strain itself expresses a broad diversity of variants over time. Thus successful superinfection would require that the secondary strain express a unique set of variants. We tested this hypothesis under conditions of natural transmission in both temperate and tropical regions where, respectively, single strain infections and strain superinfections of the tick-borne pathogen Anaplasma marginale predominate. Our conclusion that strain superinfection is associated with a significant increase in variant diversity is supported by progressive analysis of variant composition: i) animals with naturally acquired superinfection had a statistically significantly greater number of unique variant sequences as compared to animals either experimentally infected with single strains or infected with a single strain naturally; ii) the greater number of unique sequences reflected a statistically significant increase in primary structural diversity in the superinfected animals; and iii) the increase in primary structural diversity reflected increased combinations of the newly identified hypervariable micro-domains. The role of population immunity in establishing temporal and spatial patterns of infection and disease has been well-established. The results of the present study, which examined strain structure under conditions of natural transmission and population immunity, support that high levels of endemicity also drive pathogen divergence towards greater strain diversity.