Location: Animal Disease ResearchTitle: The use of the antigenically variable major surface protein 2 in the establishment of superinfection during natural tick transmission of Anaplasma marginale in southern Ghana
|KOKU, ROBERTA - Washington State University|
|FUTSE, JAMES - University Of Ghana|
|MORRISON, JILLIAN - College Of Wooster|
|BRAYTON, KELLY - Washington State University|
|PALMER, GUY - Washington State University|
Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2023
Publication Date: 3/6/2023
Citation: Koku, R., Futse, J.E., Morrison, J., Brayton, K.A., Palmer, G.H., Noh, S.M. 2023. The use of the antigenically variable major surface protein 2 in the establishment of superinfection during natural tick transmission of Anaplasma marginale in southern Ghana. Infection and Immunity. 91(4). Article e00501-22. https://doi.org/10.1128/iai.00501-22.
Interpretive Summary: Anaplasma marginale, causes bovine anaplasmosis, a production limiting disease of cattle worldwide. One hallmark of A. marginale and many other vector-borne pathogens is the ability to change the surface coat to escape the immune system and establish persistent infection, often for the life of the animal. A. marginale is also able to establish strain superinfection, defined as infection of a persistently infected host with multiple strains of the same pathogen. In effect, this increases the size of the susceptible host population even if most animals in a herd are already infected. However, it is unknown if Major Surface Protein (Msp2), the surface protein used for immune escape, also plays a role in the ability to establish superinfection. In this study, we tracked the acquisition of strains, and how variants of Msp2 were used during superinfection in a region of Southern Ghana where nearly all animals an infected with multiple strains of A. marginale. We determined that superinfection is associated with the introduction of new Msp2 gene variants, but these variants were not predominantly used to establish superinfection. These findings highlight the potential for competition among multiple strains of a pathogen for resources within the host and the balance between pathogen fitness and antigenic variation, which can ultimately lead to shifts in pathogen virulence and transmissibility.
Technical Abstract: Many vector-borne pathogens including Anaplasma spp., Borrelia spp., Trypanosoma spp., and Plasmodium spp. establish persistent infection in the mammalian host using antigenic variation. These pathogens are also able to establish strain superinfection, defined as infection of an infected host with additional strains of the same pathogen, despite an adaptive immune response. The ability to establish superinfection results in a population of susceptible hosts even with high pathogen prevalence. It is likely that antigenic variation, responsible for persistent infection, also plays a role in the establishment of superinfection. Anaplasma marginale, an antigenically variable, obligate intracellular, tick-borne, bacterial pathogen of cattle, is well-suited for the study of the role of antigenically variant surface proteins in the establishment of superinfection. Anaplasma marginale establishes persistent infection by variation in major surface protein 2 (msp2), which is encoded by approximately six donor alleles that recombine into a single expression site to produce immune escape variants. Nearly all cattle in regions of high prevalence are superinfected. By tracking the acquisition of strains in calves through time, the complement of donor alleles, and how those donor alleles are expressed we determined that simple variants derived from a single donor allele rather than multiple donor alleles were predominant. Additionally, superinfection is associated with the introduction of new donor alleles, but these new donor alleles are not predominantly used to establish superinfection. These findings highlight the potential for competition among multiple strains of a pathogen for resources within the host and the balance between pathogen fitness and antigenic variation.