title: Variant-specific and diminishing immune responses towards the highly variable MSP2(P44) outer membrane protein of Anaplasma phagocytophilum during persistent infection in lambs.
abstract: Anaplasma phagocytophilum is the causative agent of tick-borne fever in small ruminants and has been identified as the zoonotic agent of human granulocytic anaplasmosis. The Norwegian strains of the rickettsia are naturally persistent in lambs and represent a suitable experimental system for analyzing the mechanisms of persistence. Variation of the outer membrane protein MSP2(P44) by recombination of variable pseudogene segments into an expression site is believed to play a key role in persistence of the organism. The goal of the present study was to analyze the dynamics of the immune response towards A. phagocytophilum and MSP2(P44) during persistent infection of lambs. Responses to the hypervariable region of MSP2(P44) were detected shortly after appearance of the respective variants in cyclic rickettsemic peaks, consistent with a process of antigenic variation. In addition, there was a diminishing antibody response to MSP2(P44) and to other A. phagocytophilum antigens overall with time of infection, that was not associated with clearance of the infection.
authors.affiliation: Department of Production Animal Clinical Sciences, Section of Small Ruminant Research, Norwegian School of Veterinary Science, Kyrkjevegen 332/334, Sandnes N-4325, Norway. erik.georg.granquist@veths.no
authors.forename: Erik G
authors.initials: EG
authors.lastname: Granquist
authors.forename: Snorre
authors.initials: S
authors.lastname: Stuen
authors.forename: Liliana
authors.initials: L
authors.lastname: Crosby
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lundgren
authors.forename: A Rick
authors.initials: AR
authors.lastname: Alleman
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Barbet
mesh_terms: D000595:Amino Acid Sequence; D041081:Anaplasma phagocytophilum / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000940:Antigenic Variation; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D016873:Ehrlichiosis / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D005798:Genes, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D009664:Norway; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011544:Pseudogenes; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology* / Q000382:microbiology*
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D017931:DNA Primers; D010446:Peptide Fragments; D011994:Recombinant Proteins; C488283:msp2 protein, Anaplasma phagocytophilum
references.citation: Vet Microbiol. 1989 Dec;21(2):133-8
references.pmid: 2692278
references.citation: Clin Infect Dis. 2000 Aug;31(2):554-60
references.pmid: 10987720
references.citation: Res Vet Sci. 1988 Jul;45(1):28-30
references.pmid: 3222549
references.citation: Infect Immun. 2003 Apr;71(4):1706-18
references.pmid: 12654783
references.citation: J Comp Pathol. 2003 May;128(4):277-82
references.pmid: 12834611
references.citation: Res Vet Sci. 1991 Jul;51(1):40-3
references.pmid: 1680243
references.citation: J Clin Microbiol. 2003 Jul;41(7):3392-4
references.pmid: 12843101
references.citation: Infect Immun. 2008 May;76(5):2090-8
references.pmid: 18285495
references.citation: Eur J Clin Microbiol Infect Dis. 1996 Oct;15(10):829-32
references.pmid: 8950565
references.citation: Infect Immun. 2008 Jan;76(1):120-6
references.pmid: 17967854
references.citation: Vet Res Commun. 2007 Aug;31 Suppl 1:79-84
references.pmid: 17682851
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4130-5
references.pmid: 11274438
references.citation: Vet Immunol Immunopathol. 2003 Aug 15;94(3-4):163-75
references.pmid: 12909412
references.citation: Acta Vet Scand. 2001;42(3):331-8
references.pmid: 11887393
references.citation: Clin Diagn Lab Immunol. 2003 Jul;10(4):692-5
references.pmid: 12853406
references.citation: J Med Microbiol. 2008 Apr;57(Pt 4):416-423
references.pmid: 18349358
references.citation: Int J Syst Evol Microbiol. 2001 Nov;51(Pt 6):2145-2165
references.pmid: 11760958
references.citation: Infect Immun. 2007 Nov;75(11):5185-90
references.pmid: 17785476
references.citation: BMC Genomics. 2008 Jul 31;9:364
references.pmid: 18671858
references.citation: Vet Parasitol. 2008 Dec 20;158(4):344-59
references.pmid: 19028013
references.citation: Infect Immun. 2004 Dec;72(12):6852-9
references.pmid: 15557606
references.citation: Infect Immun. 2006 Nov;74(11):6429-37
references.pmid: 16966408
references.citation: BMC Microbiol. 2004 Jan 08;4:1
references.pmid: 14713314
references.citation: Clin Infect Dis. 2007 Jul 15;45 Suppl 1:S45-51
references.pmid: 17582569
references.citation: Vet Clin Pathol. 2006 Dec;35(4):418-25
references.pmid: 17123248
references.citation: Ann N Y Acad Sci. 2006 Oct;1078:446-60
references.pmid: 17114753
references.citation: Infect Immun. 2003 Sep;71(9):5324-31
references.pmid: 12933880
references.citation: Ann N Y Acad Sci. 2006 Oct;1078:236-47
references.pmid: 17114714
references.citation: PLoS Genet. 2006 Feb;2(2):e21
references.pmid: 16482227
references.citation: Mol Microbiol. 2002 Mar;43(5):1151-9
references.pmid: 11918803
references.citation: Infect Immun. 2000 Nov;68(11):6133-8
references.pmid: 11035716