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Onderstepoort Journal of Veterinary Research

versão On-line ISSN 2219-0635
versão impressa ISSN 0030-2465

Onderstepoort j. vet. res. vol.76 no.1 Cape Town  2009

 

ORIGINAL RESEARCH

 

Persistence mechanisms in tick-borne diseases

 

 

A.F. Barbet

Department of Infectious Diseases & Pathology, College of Veterinary Medicine University of Florida, Gainesville, Florida, USA

 

 


ABSTRACT

The use of new, highly sensitive diagnostic methods has revealed persistent infections to be a common feature of different tick-borne diseases, such as babesiosis, anaplasmosis and heartwater. Antigenic variation can contribute to disease persistence through the continual elaboration of new surface structures, and we know in several instances how this is achieved. Known or suspected mechanisms of persistence in babesial parasites include cytoadhesion and rapid variation of the adhesive ligand in Babesia bovis and genetic diversity in several merozoite stage proteins of different Babesia spp. In Anaplasma, extensive variation in the pfam01617 gene family accompanies cycling of organism levels in chronic infection. One result from the pioneering research at Onderstepoort is the definition of a related polymorphic gene family that is likely involved in immunity against heartwater disease. We are beginning to understand the sizes of the antigenic repertoires and full definition is close, with the possibility of applying simultaneous high-throughput sequencing to the order of 1 000 small genomes. We also, for the first time, can consider modifying these genomes and looking at effects on persistence and virulence. However, important biological questions remain unanswered; for example, why we are seeing a new emerging Anaplasma infection of humans and is infection of endothelial cells by Anaplasma significant to persistence in vivo.


 

 

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REFERENCES

AL-KHEDERY, B. & ALLRED, D.R. 2006. Antigenic variation in Babesia bovis occurs through segmental gene conversion of the ves multigene family, within a bidirectional locus of active transcription. Molecular Microbiology, 59:402-414.         [ Links ]

ALLRED, D.R. & AL KHEDERY, B. 2004. Antigenic variation and cytoadhesion in Babesia bovis and Plasmodium falciparum: different logics achieve the same goal. Molecular and Biochemical Parasitology, 134:27-35.         [ Links ]

BANKHEAD, T. & CHACONAS, G. 2007. The role of VlsE anti-genic variation in the Lyme disease spirochete: persistence through a mechanism that differs from other pathogens. Molecular Microbiology, 65:1547-1558.         [ Links ]

BARBET, A.F. & KAMPER, S.M. 1993. The importance of mosiac genes to trypanosome survival. Parasitology Today, 9:63-66.         [ Links ]

BARBET, A.F., LUNDGREN, A., YI, J., RURANGIRWA, F.R. & PALMER, G.H. 2000. Antigenic variation of Anaplasma marginale by expression of MSP2 mosaics. Infection and Immunity, 68:6133-6138.         [ Links ]

BARBET, A.F., MEEUS, P.F., BELANGER, M., BOWIE, M.V., YI, J., LUNDGREN, A.M., ALLEMAN, A.R., WONG, S.J., CHU, F.K., MUNDERLOH, U.G. & JAURON, S.D. 2003. Expression of multiple outer membrane protein sequence variants from a single genomic locus of Anaplasma phagocytophilum. Infection and Immunity, 71:1706-1718.         [ Links ]

BARBET, A.F., LUNDGREN, A.M., ALLEMAN, A.R., STUEN, S., BJOERSDORFF, A., BROWN, R.N., DRAZENOVICH, N.L. & FOLEY, J.E. 2006. Structure of the expression site reveals global diversity in MSP2 (P44) variants in Anaplasma phagocytophilum. Infection and Immunity, 74:6429-6437.         [ Links ]

BARRY, J.D., CROWE, J.S. & VICKERMAN, K. 1983. Instability of the Trypanosoma brucei rhodesiense metacyclic variable antigen repertoire. Nature, 306:699-701.         [ Links ]

BARRY, J.D. & MCCULLOCH, R. 2001. Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite. Advances in Parasitology, 49:1-70.         [ Links ]

BARRY, J.D., MARCELLO, L., MORRISON, L.J., READ, A.F., LYTHGOE, K., JONES, N., CARRINGTON, M., BLANDIN, G., BOHME, U., CALER, E., HERTZ-FOWLER, C., RENAULD, H., EL-SAYED, N. & BERRIMAN, M. 2005. What the genome sequence is revealing about trypanosome antigenic variation. Biochemical Society Transactions, 33:986-989.         [ Links ]

BEALL, M.J., CHANDRASHEKAR, R., EBERTS, M.D., CYR, K.E., DINIZ, P.P., MAINVILLE, C., HEGARTY, B.C., CRAWFORD, J.M. & BREITSCHWERDT, E.B. 2008. Serological and molecular prevalence of Borrelia burgdorferi, Anaplasma phagocytophilum, and Ehrlichia species in dogs from Minnesota. Vector-borne Zoonotic Diseases, 8:455-464.         [ Links ]

BEKKER, C.P., POSTIGO, M., TAOUFIK, A., BELL-SAKYI, L., FERRAZ, C., MARTINEZ, D. & JONGEJAN, F. 2005. Transcription analysis of the major antigenic protein 1 multigene family of three in vitro-cultured Ehrlichia ruminantium isolates. Journal of Bacteriology, 187:4782-4791.         [ Links ]

BERRIMAN, M., GHEDIN, E., HERTZ-FOWLER, C., BLANDIN, G., RENAULD, H., BARTHOLOMEU, D.C., LENNARD, N.J., CALER, E., HAMLIN, N.E., HAAS, B., BOHME, U., HANNICK, L., ASLETT, M.A., SHALLOM, J., MARCELLO, L., HOU, L., WICKSTEAD, B., ALSMARK, U.C., ARROWSMITH, C., ATKIN, R.J., BARRON, A.J., BRINGAUD, F., BROOKS, K., CARRINGTON, M., CHEREVACH, I., CHILLINGWORTH, T.J., CHURCHER, C., CLARK, L.N., CORTON, C.H., CRONIN, A., DAVIES, R.M., DOGGETT, J., DJIKENG, A., FELDBLYUM, T., FIELD, M.C., FRASER, A., GOODHEAD, I., HANCE, Z., HARPER, D., HARRIS, B.R., HAUSER, H., HOSTETLER, J., IVENS, A., JAGELS, K., JOHNSON, D., JOHNSON, J., JONES, K., KERHORNOU, A.X., KOO, H., LARKE, N., LANDFEAR, S., LARKIN, C., LEECH, V., LINE, A., LORD, A., MACLEOD, A., MOONEY, P.J., MOULE, S., MARTIN, D.M., MORGAN, G.W., MUNGALL, K., NORBERTCZAK, H., ORMOND, D., PAI, G., PEACOCK, C.S., PETERSON, J., QUAIL, M.A., RABBINOWITSCH, E., RAJANDREAM, M.A., REITTER, C., SALZBERG, S.L., SANDERS, M., SCHOBEL, S., SHARP, S., SIMMONDS, M., SIMPSON, A.J., TALLON, L., TURNER, C.M., TAIT, A., TIVEY, A.R., VAN AKEN, S., WALKER, D., WANLESS, D., WANG, S., WHITE, B., WHITE, O., WHITEHEAD, S., WOODWARD, J., WORTMAN, J., ADAMS, M.D., EMBLEY, T.M., GULL, K., ULLU, E., BARRY, J.D., FAIRLAMB, A.H., OPPERDOES, F., BARRELL, B.G., DONELSON, J.E., HALL, N., FRASER, C.M., MELVILLE, S.E. & EL SAYED, N.M. 2005. The genome of the African trypanosome Trypanosoma brucei. Science, 309:416-422.         [ Links ]

BEZUIDENHOUT, J.D., PATERSON, C.L. & BARNARD, B.J. 1985. In vitro cultivation of Cowdria ruminantium. Onderstepoort Journal of Veterinary Research, 52:113-120.         [ Links ]

BORST, P. 2002. Antigenic variation and allelic exclusion. Cell, 109:5-8.         [ Links ]

BRAYTON, K.A., KNOWLES, D.P., McGUIRE, T.C. & PALMER, G.H. 2001. Efficient use of a small genome to generate antigenic diversity in tick-borne ehrlichial pathogens. Proceedings of the National Academy of Science USA, 98:4130-4135.         [ Links ]

BRAYTON, K.A., MEEUS, P.F., BARBET, A.F. & PALMER, G.H. 2003. Simultaneous variation of the immunodominant outer membrane proteins, MSP2 and MSP3, during Anaplasma marginale persistence in vivo. Infection and Immunity, 71: 6627-6632.         [ Links ]

BRAYTON, K.A., LAU, A.O.T., HERNDON, D.R., HANNICK, L., KAPPMEYER, L.S., BERENS, S.J., BIDWELL, S.L., BROWN, W.C., CRABTREE, J., FADROSH, D., FELDBLUM, T., FORBERGER, H.A., HAAS, B.J., HOWELL, J.M., KHOURI, H., KOO, H., MANN, D.J., NORIMINE, J., PAULSEN, I.T., RADUNE, D., REN, Q., SMITH, R.K. (Jr), SUAREZ, C.E., WHITE, O., WORTMAN, J.R., KNOWLES, D.P. (Jr), McELWAIN, T.F. & NENE, V.M. 2007. Genome sequence of Babesia bovis and comparative analysis of apicomplexan hemoprotozoa. PLoS Pathogens, 3:e148.         [ Links ]

BURGDORFER, W. & MAVROS, A.J. 1970. Susceptibility of various species of rodents to the Relapsing Fever spirochete, Borrelia hermsii. Infection and Immunity, 2:256-259.         [ Links ]

CALDER, J.A., REDDY, G.R., CHIEVES, L., COURTNEY, C.H., LITTELL, R., LIVENGOOD, J.R., NORVAL, R.A., SMITH, C. & DAME, J.B. 1996. Monitoring Babesia bovis infections in cattle by using PCR-based tests. Journal of Clinical Microbiology, 34:2748-2755.         [ Links ]

COLLINS, N.E., LIEBENBERG, J., DE VILLIERS, E.P., BRAYTON, K.A., LOUW, E., PRETORIUS, A., FABER, F.E., VAN HEERDEN, H., JOSEMANS, A., VAN KLEEF, M., STEYN, H.C., VAN STRIJP, M.F., ZWEYGARTH, E., JONGEJAN, F., MAILLARD, J.C., BERTHIER, D., BOTHA, M., JOUBERT, F., CORTÓN, C.H., THOMSON, N.R., ALLSOPP, M.T. & ALLSOPP, B.A. 2005. The genome of the heartwater agent Ehrlichia ruminantium contains multiple tandem repeats of actively variable copy number. Proceedings of the National Academy of Science USA,102:838-843.         [ Links ]

DUMLER, J.S., CHOI, K., GARCIA-GARCIA, J.C., BARAT, N.S., SCORPIO, D.G., GARYU, J.W., GRAB, D.J. & BAKKEN, J.S. 2005. Human granulocytic anaplasmosis and Anaplasma phagocytophilum. Emerging Infectious Diseases, 11:1828-1834.         [ Links ]

DUMLER, J.S., BARAT, N.C., BARAT, C.E. & BAKKEN, J.S. 2007. Human granulocytic anaplasmosis and macrophage activation. Clinical Infectious Diseases 45:199-204.         [ Links ]

DUNNING HOTOPP, J.C., LIN, M., MADUPU, R., CRABTREE, J., ANGIUOLI, S.V., EISEN, J., SESHADRI, R., REN, Q., WU, M., UTTERBACK, T.R., SMITH, S., LEWIS, M., KHOURI, H., ZHANG, C., NIU, H., LIN, Q., OHASHI, N., ZHI, N., NELSON, W., BRINKAC, L.M., DODSON, R.J., ROSOVITZ, M.J., SUNDARAM, J., DAUGHERTY, S.C., DAVIDSEN, T., DURKIN, A.S., GWINN, M., HAFT, D.H., SELENGUT, J.D., SULLIVAN, S.A., ZAFAR, N., ZHOU, L., BENAHMED, F., FORBERGER, H., HALPIN, R., MULLIGAN, S., ROBINSON, J., WHITE, O., RIKIHISA, Y. & TETTELIN, H. 2006. Comparative genomics of emerging human ehrlichiosis agents. PLoS.Genetics, 2:e21.         [ Links ]

FELSHEIM, R.F., HERRON, M.J., NELSON, C. M., BURKHARDT, N.Y., BARBET, A.F., KURTTI, T.J. & MUNDERLOH, U.G. 2006. Transformation of Anaplasma phagocytophilum. BMC. Biotechnology, 6:42.         [ Links ]

FRUTOS, R., VIARI, A., FERRAZ, C., MORGAT, A., EYCHENIE, S., KANDASSAMY, Y., CHANTAL, I., BENSAID, A., COISSAC, E., VACHIERY, N., DEMAILLE, J. & MARTINEZ, D. 2006. Comparative genomic analysis of three strains of Ehrlichia ruminantium reveals an active process of genome size plasticity. Journal of Bacteriology, 188:2533-2542.         [ Links ]

FUTSE, J.E., BRAYTON, K.A., DARK, M.J., KNOWLES, D.P. (Jr) & PALMER, G.H. 2008. Superinfection as a driver of genomic diversification in antigenically variant pathogens. Proceedings of the National Academy of Science USA, 105: 2123-2127.         [ Links ]

GE, Y. & RIKIHISA, Y. 2007. Surface-exposed proteins of Ehrlichia chaffeensis. Infection and Immunity, 75:3604-3613.         [ Links ]

GRANQUIST, E.G., STUEN, S., LUNDGREN, A.M., BRATEN, M. & BARBET, A.F. 2008. Outer membrane protein sequence variation in lambs experimentally infected with Anaplasma phagocytophilum. Infection and Immunity, 76:120-126.         [ Links ]

HOLT, R.A. & JONES, S.J. 2008. The new paradigm of flow cell sequencing. Genome Research, 18:839-846.         [ Links ]

HORN, D. 2004. The molecular control of antigenic variation in Trypanosoma brucei. Current Molecular Medicine, 4:563-576.         [ Links ]

HUTCHINSON, O.C., PICOZZI, K., JONES, N.G., MOTT, H., SHARMA, R., WELBURN, S.C. & CARRINGTON, M. 2007. Variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific. BMC. Genomics, 8:234.         [ Links ]

JENSEN, J., SIMON, D., MURUA, E.H., SOLLER, J.T., BULLERDIEK, J., BEELITZ, P., PFISTER, K. & NOLTE, I. 2007. Anaplasma phagocytophilum in dogs in Germany. Zoonoses and Public Health, 54:94-101.         [ Links ]

JONGEJAN, F., THIELEMANS, M.J., BRIERE, C. & UILENBERG, G. 1991. Antigenic diversity of Cowdria ruminantium isolates determined by cross-immunity. Research in Veterinary Science, 51:24-28.         [ Links ]

JONGEJAN, F., VOGEL, S.W., GUEYE, A. & UILENBERG, G. 1993. Vaccination against heartwater using in vitro attenuated Cowdria ruminantium organisms. Revue d'Elevage et de Medicine Veterinaire des Pays Tropicaux, 46:223-227.         [ Links ]

KAMPER, S.M. & BARBET, A.F. 1992. Surface epitope variation via mosaic gene formation is potential key to long-term survival of Trypanosoma brucei. Molecular and Biochemical Parasitology, 53:33-44.         [ Links ]

KIESER, S.T., ERIKS, I.S. & PALMER, G.H. 1990. Cyclic rickettsemia during persistent Anaplasma marginale infection of cattle. Infection and Immunity, 58:1117-1119.         [ Links ]

KOHN, B., GALKE, D., BEELITZ, P. & PFISTER, K. 2008. Clinical features of canine granulocytic anaplasmosis in 18 naturally infected dogs. Journal of Veterinary Internal Medicine, 22:1289-1295.         [ Links ]

LESTER, S.J., BREITSCHWERDT, E.B., COLLIS, C.D. & HEGARTY, B.C. 2005. Anaplasma phagocytophilum infection (granulocytic anaplasmosis) in a dog from Vancouver Island. Canadian Veterinary Journal, 46:825-827.         [ Links ]

LIN, Q. & RIKIHISA, Y. 2005. Establishment of cloned Anaplasma phagocytophilum and analysis of p44 gene conversion within an infected horse and infected SCID mice. Infection and Immunity, 73:5106-5114.         [ Links ]

MAGNUS, E., VERVOORT, T. & VAN MEIRVENNE, N. 1982. Serological cross-reactions among trypanosome variable antigen isotypes of the subgenus Trypanozoon. Annales de la Societe belge de Medicine tropicale, 62:25-39.         [ Links ]

MAHAN, S.M., ALLSOPP, B., KOCAN, K.M., PALMER, G.H. & JONGEJAN, F. 1999. Vaccine strategies for Cowdria ruminantium infections and their application to other ehrlichial infections. Parasitology Today, 15:290-294.         [ Links ]

MARCELLO, L. & BARRY, J.D. 2007. Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure. Genome Research, 17: 1344-1352.         [ Links ]

MARGULIES, M., EGHOLM, M., ALTMAN, W.E., ATTIYA, S., BADER, J.S., BEMBEN, L.A., BERKA, J., BRAVERMAN, M.S., CHEN, Y.J., CHEN, Z., DEWELL, S.B., DU, L., FIERRO, J.M., GOMES, X.V., GODWIN, B.C., HE, W., HELGESEN, S., HO, C.H., IRZYK, G.P., JANDO, S.C., ALENQUER, M.L., JARVIE, T.P., JIRAGE, K.B., KIM, J.B., KNIGHT, J.R., LANZA, J.R., LEAMON, J.H., LEFKOWITZ, S.M., LEI, M., LI, J., LOHMAN, K.L., LU, H., MAKHIJANI, V.B., MCDADE, K.E., MCKENNA, M.P., MYERS, E.W., NICKERSON, E., NOBILE, J.R., PLANT, R., PUC, B.P., RONAN, M.T., ROTH, G.T., SARKIS, G.J., SIMONS, J.F., SIMPSON, J.W., SRINIVASAN, M., TARTARO, K.R., TOMASZ, A., VOGT, K.A., VOLKMER, G.A., WANG, S.H., WANG, Y., WEINER, M.P., YU, P., BEGLEY, R.F. & ROTHBERG, J.M. 2005. Genome sequencing in microfabricated high-density picolitre reactors. Nature, 437:376-380.         [ Links ]

MCCULLOCH, R. 2004. Antigenic variation in African trypanosomes: monitoring progress. Trends in Parasitology, 20:117-121.         [ Links ]

MEEUS, P.F., BRAYTON, K.A., PALMER, G.H. & BARBET, A.F. 2003. Conservation of a gene conversion mechanism in two distantly related paralogues of Anaplasma marginale. Molecular Microbiology, 47:633-643.         [ Links ]

MUNDERLOH, U.G., LYNCH, M.J., HERRON, M.J., PALMER, A.T., KURTTI, T.J., NELSON, R.D. & GOODMAN, J.L. 2004. Infection of endothelial cells with Anaplasma marginale and A. phagocytophilum. Veterinary Microbiology, 101:53-64.         [ Links ]

NYIKA, A., MAHAN, S.M., BURRIDGE, M.J., McGUIRE, T.C., RURANGIRWA, F. & BARBET, A.F. 1998. A DNA vaccine protects mice against the rickettsial agent Cowdria ruminantium. Parasite Immunology, 20:111-119.         [ Links ]

NYIKA, A., BARBET, A.F., BURRIDGE, M.J. & MAHAN, S.M. 2002. DNA vaccination with map1 gene followed by protein boost augments protection against challenge with Cowdria ruminantium, the agent of heartwater. Vaccine, 20:1215-1225.         [ Links ]

O'CONNOR, R.M., LANE, T.J., STROUP, S.E. & ALLRED, D.R. 1997. Characterization of a variant erythrocyte surface antigen (VESA1) expressed by Babesia bovis during antigenic variation. Molecular and Biochemical Parasitology, 89:259-270.         [ Links ]

O'CONNOR, R.M., LONG, J.A. & ALLRED, D.R. 1999. Cytoadherence of Babesia bovis-infected erythrocytes to bovine brain capillary endothelial cells provides an in vitro model for sequestration. Infection and Immunity, 67:3921-3928.         [ Links ]

PALMER, G.H., OBERLE, S.M., BARBET, A.F., GOFF, W.L., DAVIS, W.C. & MCGUIRE, T.C. 1988. Immunization of cattle with a 36-kilodalton surface protein induces protection against homologous and heterologous Anaplasma marginale challenge. Infection and Immunity, 56:1526-1531.         [ Links ]

PALMER, G.H., FUTSE, J.E., KNOWLES, D.P. (Jr) & BRAYTON, K.A. 2006. Insights into mechanisms of bacterial antigenic variation derived from the complete genome sequence of Anaplasma marginale. Annals of the New York Academy of Science 1078:15-25.         [ Links ]

PAYS, E., VANHAMME, L. & PEREZ-MORGA, D. 2004. Anti-genic variation in Trypanosoma brucei: facts, challenges and mysteries. Current Opinions in Microbiology, 7:369-374.         [ Links ]

POITOUT, F.M., SHINOZAKI, J.K., STOCKWELL, P.J., HOLLAND, C.J. & SHUKLA, S.K. 2005. Genetic variants of Ana-plasma phagocytophilum infecting dogs in Western Washington State. Journal of Clinical Microbiology, 43:796-801.         [ Links ]

POSTIGO, M., TAOUFIK, A., BELL-SAKYI, L., BEKKER, C.P., DE, V.E., MORRISON, W.I. & JONGEJAN, F. 2008. Host cell-specific protein expression in vitro in Ehrlichia ruminantium. Veterinary Microbiology, 128:136-147.         [ Links ]

REDDY, G.R., SULSONA, C.R., HARRISON, R.H., MAHAN, S.M., BURRIDGE, M.J. & BARBET, A.F. 1996. Sequence heterogeneity of the major antigenic protein 1 genes from Cowdria ruminantium isolates from different geographical areas. Clinical and Diagnostic Laboratory: Immunology, 3:417-422.         [ Links ]

RODRIGUEZ, J.L., PALMER, G.H., KNOWLES, D.P. (Jr) & BRAYTON, K.A. 2005. Distinctly different msp2 pseudogene repertoires in Anaplasma marginale strains that are capable of superinfection. Gene, 361:127-132.         [ Links ]

ROTH, C., BRINGAUD, F., LAYDEN, R., BALTZ, T. & EISEN, H. 1989. Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes. Proceedings of the National Academy of Sciences USA, 86:9375-9379.         [ Links ]

SEO, G.M., CHENG, C., TOMICH, J. & GANTA, R.R. 2008. Total, membrane, and immunogenic proteomes of macrophage and tick cell-derived Ehrlichia chaffeensis evaluated by LC-MS/MS and MALDI-TOF methods. Infection and Immunity, 76:4823-4832        [ Links ]

STUEN, S. 2007. Anaplasma phagocytophilum-the most widespread tick-borne infection in animals in Europe. Veterinary Research Communications, 31, Suppl. 1:79-84.         [ Links ]

VAN HEERDEN, H., COLLINS, N.E., BRAYTON, K.A., RADEMEYER, C. & ALLSOPP, B.A. 2004. Characterization of a major outer membrane protein multigene family in Ehrlichia ruminantium. Gene, 330:159-168.         [ Links ]

VANHAMME, L., PAYS, E., MCCULLOCH, R. & BARRY, J.D. 2001. An update on antigenic variation in African trypanosomes. Trends in Parasitology, 17:338-343.         [ Links ]

VERVOORT, T., BARBET, A.F., MUSOKE, A.J., MAGNUS, E., MPIMBAZA, G. & VAN MEIRVENNE, N. 1981. Isotypic surface glycoproteins of trypanosomes. Immunology 44:223-232.         [ Links ]

WAMSLEY, H.L. & BARBET, A.F. 2008. In situ detection of Anaplasma spp. by DNA target-primed rolling-circle amplification of a padlock probe and intracellular colocalization with immunofluorescently labeled host cell von Willebrand factor. Journal of Clinical Microbiology, 46:2314-2319.         [ Links ]

WANG, X., RIKIHISA, Y., LAI, T.H., KUMAGAI, Y., ZHI, N. & REED, S.M. 2004. Rapid sequential changeover of expressed p44 genes during the acute phase of Anaplasma phagocytophilum infection in horses. Infection and Immunity, 72: 6852-6859.         [ Links ]

WANG, X., KIKUCHI, T. & RIKIHISA, Y. 2006. Two monoclonal antibodies with defined epitopes of P44 major surface proteins neutralize Anaplasma phagocytophilum by distinct mechanisms. Infection and Immunity, 74:1873-1882.         [ Links ]

YAGER, E., BITSAKTSIS, C., NANDI, B., MCBRIDE, J.W. & WINSLOW, G. 2005. Essential role for humoral immunity during Ehrlichia infection in immunocompetent mice. Infection and Immunity, 73:8009-8016.         [ Links ]

ZHENG, Y.H., SENTSUI, H., NAKAYA, T., KONO, Y. & IKUTA, K. 1997. In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain. Journal of Virology, 71: 5031-5039.         [ Links ]

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