title: Antigen variability in Anaplasma phagocytophilum during chronic infection of a reservoir host.
abstract: Anaplasma phagocytophilum is an obligately intracellular, tick-transmitted, bacterial pathogen of humans and other animals. In order to evade host immunity during the course of infection, A. phagocytophilum utilizes gene conversion to shuffle approximately 100 functional pseudogenes into a single expression cassette of the msp2(p44) gene, which encodes the major surface antigen, major surface protein 2 (Msp2). The role and extent of msp2(p44) recombination in a reservoir host for A. phagocytophilum have not been evaluated. In the current study, we explored patterns of recombination and expression site variability of the msp2(p44) gene in three chronically infected woodrats, a reservoir for the disease in the Western USA. All three woodrats developed persistent infection of at least 6 months duration; two of them maintained active infection for at least 8 months. In total, we detected the emergence of 60 unique msp2(p44) expression site variants with no common temporal patterns of expression site recombination among the three A. phagocytophilum populations. Both the strength of infection (i.e. pathogen load) and the genetic diversity of pseudogenes detected at the msp2(p44) expression site fluctuated periodically during the course of infection. An analysis of the genomic pseudogene exhaustion rate showed that the repertoire of pseudogenes available to the A. phagocytophilum population could in theory become depleted within a year. However, the apparent emergence of variant pseudogenes suggests that the pathogen could potentially evade host immunity indefinitely. Our findings suggest a tightly co-evolved relationship between A. phagocytophilum and woodrats in which the pathogen perpetually evades host immunity yet causes no detectable disease.
authors.affiliation: University of California, Davis School of Veterinary Medicine, Department of Medicine and Epidemiology, Davis, CA 95616, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rejmanek
authors.affiliation: California State University Department of Biological Sciences, Sacramento, CA 95819, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Foley
authors.affiliation: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Barbet
authors.affiliation: University of California, Davis School of Veterinary Medicine, Department of Medicine and Epidemiology, Davis, CA 95616, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Foley
mesh_terms: D041081:Anaplasma phagocytophilum / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D000818:Animals; D000940:Antigenic Variation; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D002908:Chronic Disease; D004197:Disease Reservoirs / Q000382:microbiology*; D016873:Ehrlichiosis / Q000276:immunology* / Q000382:microbiology; D019143:Evolution, Molecular; D005260:Female; D008297:Male; D008969:Molecular Sequence Data; D011544:Pseudogenes; D011995:Recombination, Genetic; D012376:Rodent Diseases / Q000276:immunology* / Q000382:microbiology; D017422:Sequence Analysis, DNA; D016205:Sigmodontinae / Q000382:microbiology
chemical_list: D001425:Bacterial Outer Membrane Proteins; C488283:msp2 protein, Anaplasma phagocytophilum