Variant-specific and diminishing immune responses towards the highly variable MSP2(P44) outer membrane protein of Anaplasma phagocytophilum during persistent infection in lambs.
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.
Granquist
Erik G
EG
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
Stuen
Snorre
S
Crosby
Liliana
L
Lundgren
Anna M
AM
Alleman
A Rick
AR
Barbet
Anthony F
AF
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*
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D017931:DNA Primers; D010446:Peptide Fragments; D011994:Recombinant Proteins; C488283:msp2 protein, Anaplasma phagocytophilum
Vet Microbiol. 1989 Dec;21(2):133-8
2692278
Clin Infect Dis. 2000 Aug;31(2):554-60
10987720
Res Vet Sci. 1988 Jul;45(1):28-30
3222549
Infect Immun. 2003 Apr;71(4):1706-18
12654783
J Comp Pathol. 2003 May;128(4):277-82
12834611
Res Vet Sci. 1991 Jul;51(1):40-3
1680243
J Clin Microbiol. 2003 Jul;41(7):3392-4
12843101
Infect Immun. 2008 May;76(5):2090-8
18285495
Eur J Clin Microbiol Infect Dis. 1996 Oct;15(10):829-32
8950565
Infect Immun. 2008 Jan;76(1):120-6
17967854
Vet Res Commun. 2007 Aug;31 Suppl 1:79-84
17682851
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4130-5
11274438
Vet Immunol Immunopathol. 2003 Aug 15;94(3-4):163-75
12909412
Acta Vet Scand. 2001;42(3):331-8
11887393
Clin Diagn Lab Immunol. 2003 Jul;10(4):692-5
12853406
J Med Microbiol. 2008 Apr;57(Pt 4):416-423
18349358
Int J Syst Evol Microbiol. 2001 Nov;51(Pt 6):2145-2165
11760958
Infect Immun. 2007 Nov;75(11):5185-90
17785476
BMC Genomics. 2008 Jul 31;9:364
18671858
Vet Parasitol. 2008 Dec 20;158(4):344-59
19028013
Infect Immun. 2004 Dec;72(12):6852-9
15557606
Infect Immun. 2006 Nov;74(11):6429-37
16966408
BMC Microbiol. 2004 Jan 08;4:1
14713314
Clin Infect Dis. 2007 Jul 15;45 Suppl 1:S45-51
17582569
Vet Clin Pathol. 2006 Dec;35(4):418-25
17123248
Ann N Y Acad Sci. 2006 Oct;1078:446-60
17114753
Infect Immun. 2003 Sep;71(9):5324-31
12933880
Ann N Y Acad Sci. 2006 Oct;1078:236-47
17114714
PLoS Genet. 2006 Feb;2(2):e21
16482227
Mol Microbiol. 2002 Mar;43(5):1151-9
11918803
Infect Immun. 2000 Nov;68(11):6133-8
11035716