This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by French, D. M.
Right arrow Articles by Palmer, G. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by French, D. M.
Right arrow Articles by Palmer, G. H.

 Previous Article  |  Next Article 

Infection and Immunity, November 1999, p. 5834-5840, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Emergence of Anaplasma marginale Antigenic Variants during Persistent Rickettsemia

Dorothy M. French, Wendy C. Brown, and Guy H. Palmer*

Program in Vector-Borne Diseases, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040

Received 7 April 1999/Returned for modification 14 June 1999/Accepted 18 August 1999

Anaplasma marginale is an ehrlichial pathogen of cattle, in the order Rickettsiales, that establishes persistent cyclic rickettsemia in the infected host. Within each rickettsemic cycle, A. marginale expressing antigenically variant major surface protein 2 (MSP2) emerge. By cloning 17 full-length msp2 transcripts expressed during cyclic rickettsemia, we determined that emergent variants have a single, central hypervariable region encoding variant B-cell epitopes. The N- and C-terminal regions are highly conserved among the expressed A. marginale variants, and similar sequences define the MSP2 homologues in the agent of human granulocytic ehrlichiosis (HGE). This is in contrast to the MSP2 homologues in ehrlichial genogroup I pathogens, Ehrlichia chaffeensis, Ehrlichia canis, and Cowdria ruminantium, that have multiple hypervariable regions. By defining the variable and conserved regions, we were able to show that the single hypervariable region of A. marginale MSP2 encodes epitopes that are immunogenic and induce variant-specific antibody responses during persistent infection. These findings demonstrate that the MSP2 structural variants that emerge during each cycle of persistent rickettsemia are true antigenic variants, consistent with MSP2 antigenic variation as a mechanism of A. marginale persistence.

* Corresponding author. Mailing address: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040. Phone: (509) 335-6033. Fax: (509) 335-8529. E-mail: gpalmer{at}vetmed.wsu.edu.

Infection and Immunity, November 1999, p. 5834-5840, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Futse, J. E., Brayton, K. A., Nydam, S. D., Palmer, G. H. (2009). Generation of Antigenic Variants via Gene Conversion: Evidence for Recombination Fitness Selection at the Locus Level in Anaplasma marginale. Infect. Immun. 77: 3181-3187 [Abstract] [Full Text]  
  • Barbet, A. F., Byrom, B., Mahan, S. M. (2009). Diversity of Ehrlichia ruminantium Major Antigenic Protein 1-2 in Field Isolates and Infected Sheep. Infect. Immun. 77: 2304-2310 [Abstract] [Full Text]  
  • Han, S., Norimine, J., Palmer, G. H., Mwangi, W., Lahmers, K. K., Brown, W. C. (2008). Rapid Deletion of Antigen-Specific CD4+ T Cells following Infection Represents a Strategy of Immune Evasion and Persistence for Anaplasma marginale. J. Immunol. 181: 7759-7769 [Abstract] [Full Text]  
  • 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. Proc. Natl. Acad. Sci. USA 105: 2123-2127 [Abstract] [Full Text]  
  • 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. Infect. Immun. 76: 120-126 [Abstract] [Full Text]  
  • Zhuang, Y., Futse, J. E., Brown, W. C., Brayton, K. A., Palmer, G. H. (2007). Maintenance of Antibody to Pathogen Epitopes Generated by Segmental Gene Conversion Is Highly Dynamic during Long-Term Persistent Infection. Infect. Immun. 75: 5185-5190 [Abstract] [Full Text]  
  • Palmer, G. H., Futse, J. E., Leverich, C. K., Knowles, D. P. Jr., Rurangirwa, F. R., Brayton, K. A. (2007). Selection for Simple Major Surface Protein 2 Variants during Anaplasma marginale Transmission to Immunologically Naive Animals. Infect. Immun. 75: 1502-1506 [Abstract] [Full Text]  
  • 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. Infect. Immun. 74: 6429-6437 [Abstract] [Full Text]  
  • Macmillan, H., Brayton, K. A., Palmer, G. H., McGuire, T. C., Munske, G., Siems, W. F., Brown, W. C. (2006). Analysis of the Anaplasma marginale Major Surface Protein 1 Complex Protein Composition by Tandem Mass Spectrometry. J. Bacteriol. 188: 4983-4991 [Abstract] [Full Text]  
  • Noh, S. M., Brayton, K. A., Knowles, D. P., Agnes, J. T., Dark, M. J., Brown, W. C., Baszler, T. V., Palmer, G. H. (2006). Differential Expression and Sequence Conservation of the Anaplasma marginale msp2 Gene Superfamily Outer Membrane Proteins.. Infect. Immun. 74: 3471-3479 [Abstract] [Full Text]  
  • Lopez, J. E., Siems, W. F., Palmer, G. H., Brayton, K. A., McGuire, T. C., Norimine, J., Brown, W. C. (2005). Identification of Novel Antigenic Proteins in a Complex Anaplasma marginale Outer Membrane Immunogen by Mass Spectrometry and Genomic Mapping. Infect. Immun. 73: 8109-8118 [Abstract] [Full Text]  
  • Abbott, J. R., Palmer, G. H., Kegerreis, K. A., Hetrick, P. F., Howard, C. J., Hope, J. C., Brown, W. C. (2005). Rapid and Long-Term Disappearance of CD4+ T Lymphocyte Responses Specific for Anaplasma Marginale Major Surface Protein-2 (MSP2) in MSP2 Vaccinates following Challenge with Live A. marginale. J. Immunol. 174: 6702-6715 [Abstract] [Full Text]  
  • Brayton, K. A., Kappmeyer, L. S., Herndon, D. R., Dark, M. J., Tibbals, D. L., Palmer, G. H., McGuire, T. C., Knowles, D. P. Jr. (2005). Complete genome sequencing of Anaplasma marginale reveals that the surface is skewed to two superfamilies of outer membrane proteins. Proc. Natl. Acad. Sci. USA 102: 844-849 [Abstract] [Full Text]  
  • Singu, V., Liu, H., Cheng, C., Ganta, R. R. (2005). Ehrlichia chaffeensis Expresses Macrophage- and Tick Cell-Specific 28-Kilodalton Outer Membrane Proteins. Infect. Immun. 73: 79-87 [Abstract] [Full Text]  
  • 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. Infect. Immun. 72: 6852-6859 [Abstract] [Full Text]  
  • Stich, R. W., Olah, G. A., Brayton, K. A., Brown, W. C., Fechheimer, M., Green-Church, K., Jittapalapong, S., Kocan, K. M., McGuire, T. C., Rurangirwa, F. R., Palmer, G. H. (2004). Identification of a Novel Anaplasma marginale Appendage-Associated Protein That Localizes with Actin Filaments during Intraerythrocytic Infection. Infect. Immun. 72: 7257-7264 [Abstract] [Full Text]  
  • Abbott, J. R., Palmer, G. H., Howard, C. J., Hope, J. C., Brown, W. C. (2004). Anaplasma marginale Major Surface Protein 2 CD4+-T-Cell Epitopes Are Evenly Distributed in Conserved and Hypervariable Regions (HVR), Whereas Linear B-Cell Epitopes Are Predominantly Located in the HVR. Infect. Immun. 72: 7360-7366 [Abstract] [Full Text]  
  • Brown, W. C., Palmer, G. H., Brayton, K. A., Meeus, P. F. M., Barbet, A. F., Kegerreis, K. A., McGuire, T. C. (2004). CD4+ T Lymphocytes from Anaplasma marginale Major Surface Protein 2 (MSP2) Vaccinees Recognize Naturally Processed Epitopes Conserved in MSP3. Infect. Immun. 72: 3688-3692 [Abstract] [Full Text]  
  • Felek, S., Telford, S. III, Falco, R. C., Rikihisa, Y. (2004). Sequence Analysis of p44 Homologs Expressed by Anaplasma phagocytophilum in Infected Ticks Feeding on Naive Hosts and in Mice Infected by Tick Attachment. Infect. Immun. 72: 659-666 [Abstract] [Full Text]  
  • Brayton, K. A., Meeus, P. F. M., Barbet, A. F., Palmer, G. H. (2003). Simultaneous Variation of the Immunodominant Outer Membrane Proteins, MSP2 and MSP3, during Anaplasma marginale Persistence In Vivo. Infect. Immun. 71: 6627-6632 [Abstract] [Full Text]  
  • Kocan, K. M., de la Fuente, J., Guglielmone, A. A., Melendez, R. D. (2003). Antigens and Alternatives for Control of Anaplasma marginale Infection in Cattle. Clin. Microbiol. Rev. 16: 698-712 [Abstract] [Full Text]  
  • Li, J. S.-y., Winslow, G. M. (2003). Survival, Replication, and Antibody Susceptibility of Ehrlichia chaffeensis outside of Host Cells. Infect. Immun. 71: 4229-4237 [Abstract] [Full Text]  
  • Futse, J. E., Ueti, M. W., Knowles, D. P. Jr., Palmer, G. H. (2003). Transmission of Anaplasma marginale by Boophilus microplus: Retention of Vector Competence in the Absence of Vector-Pathogen Interaction. J. Clin. Microbiol. 41: 3829-3834 [Abstract] [Full Text]  
  • Park, J., Choi, K. S., Dumler, J. S. (2003). Major Surface Protein 2 of Anaplasma phagocytophilum Facilitates Adherence to Granulocytes. Infect. Immun. 71: 4018-4025 [Abstract] [Full Text]  
  • Barbet, A. F., Meeus, P. F. M., 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. Infect. Immun. 71: 1706-1718 [Abstract] [Full Text]  
  • Brown, W. C., Brayton, K. A., Styer, C. M., Palmer, G. H. (2003). The Hypervariable Region of Anaplasma marginale Major Surface Protein 2 (MSP2) Contains Multiple Immunodominant CD4+ T Lymphocyte Epitopes That Elicit Variant-Specific Proliferative and IFN-{gamma} Responses in MSP2 Vaccinates. J. Immunol. 170: 3790-3798 [Abstract] [Full Text]  
  • Lohr, C. V., Brayton, K. A., Shkap, V., Molad, T., Barbet, A. F., Brown, W. C., Palmer, G. H. (2002). Expression of Anaplasma marginale Major Surface Protein 2 Operon-Associated Proteins during Mammalian and Arthropod Infection. Infect. Immun. 70: 6005-6012 [Abstract] [Full Text]  
  • Brown, W. C., McGuire, T. C., Mwangi, W., Kegerreis, K. A., Macmillan, H., Lewin, H. A., Palmer, G. H. (2002). Major Histocompatibility Complex Class II DR-Restricted Memory CD4+ T Lymphocytes Recognize Conserved Immunodominant Epitopes of Anaplasma marginale Major Surface Protein 1a. Infect. Immun. 70: 5521-5532 [Abstract] [Full Text]  
  • IJdo, J. W., Wu, C., Telford III, S. R., Fikrig, E. (2002). Differential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis. Infect. Immun. 70: 5295-5298 [Abstract] [Full Text]  
  • Caspersen, K., Park, J.-H., Patil, S., Dumler, J. S. (2002). Genetic Variability and Stability of Anaplasma phagocytophila msp2 (p44). Infect. Immun. 70: 1230-1234 [Abstract] [Full Text]  
  • Shkap, V., Molad, T., Brayton, K. A., Brown, W. C., Palmer, G. H. (2002). Expression of Major Surface Protein 2 Variants with Conserved T-Cell Epitopes in Anaplasma centrale Vaccinates. Infect. Immun. 70: 642-648 [Abstract] [Full Text]  
  • Lohr, C. V., Rurangirwa, F. R., McElwain, T. F., Stiller, D., Palmer, G. H. (2002). Specific Expression of Anaplasma marginale Major Surface Protein 2 Salivary Gland Variants Occurs in the Midgut and Is an Early Event during Tick Transmission. Infect. Immun. 70: 114-120 [Abstract] [Full Text]  
  • de la Fuente, J., Kocan, K. M. (2001). Expression of Anaplasma marginale Major Surface Protein 2 Variants in Persistently Infected Ticks. Infect. Immun. 69: 5151-5156 [Abstract] [Full Text]  
  • Lodes, M. J., Mohamath, R., Reynolds, L. D., McNeill, P., Kolbert, C. P., Bruinsma, E. S., Benson, D. R., Hofmeister, E., Reed, S. G., Houghton, R. L., Persing, D. H. (2001). Serodiagnosis of Human Granulocytic Ehrlichiosis by Using Novel Combinations of Immunoreactive Recombinant Proteins. J. Clin. Microbiol. 39: 2466-2476 [Abstract] [Full Text]  
  • Barbet, A. F., Yi, J., Lundgren, A., McEwen, B. R., Blouin, E. F., Kocan, K. M. (2001). Antigenic Variation of Anaplasma Marginale: Major Surface Protein 2 Diversity during Cyclic Transmission between Ticks and Cattle. Infect. Immun. 69: 3057-3066 [Abstract] [Full Text]  
  • Liang, F. T., Bowers, L. C., Philipp, M. T. (2001). C-Terminal Invariable Domain of VlsE Is Immunodominant but Its Antigenicity Is Scarcely Conserved among Strains of Lyme Disease Spirochetes. Infect. Immun. 69: 3224-3231 [Abstract] [Full Text]  
  • Martin, M. E., Caspersen, K., Dumler, J. S. (2001). Immunopathology and Ehrlichial Propagation Are Regulated by Interferon-{{gamma}} and Interleukin-10 in a Murine Model of Human Granulocytic Ehrlichiosis. Am. J. Pathol. 158: 1881-1888 [Abstract] [Full Text]  
  • Semu, S. M., Peter, T. F., Mukwedeya, D., Barbet, A. F., Jongejan, F., Mahan, S. M. (2001). Antibody Responses to MAP 1B and Other Cowdria ruminantium Antigens Are Down Regulated in Cattle Challenged with Tick-Transmitted Heartwater. CVI 8: 388-396 [Abstract] [Full Text]  
  • Palmer, G. H., Rurangirwa, F. R., McElwain, T. F. (2001). Strain Composition of the Ehrlichia Anaplasma marginale within Persistently Infected Cattle, a Mammalian Reservoir for Tick Transmission. J. Clin. Microbiol. 39: 631-635 [Abstract] [Full Text]  
  • Shu-yi Li, J., Yager, E., Reilly, M., Freeman, C., Reddy, G. R., Reilly, A. A., Chu, F. K., Winslow, G. M. (2001). Outer Membrane Protein-Specific Monoclonal Antibodies Protect SCID Mice from Fatal Infection by the Obligate Intracellular Bacterial Pathogen Ehrlichia chaffeensis. J. Immunol. 166: 1855-1862 [Abstract] [Full Text]  
  • Brown, W. C., McGuire, T. C., Zhu, D., Lewin, H. A., Sosnow, J., Palmer, G. H. (2001). Highly Conserved Regions of the Immunodominant Major Surface Protein 2 of the Genogroup II Ehrlichial Pathogen Anaplasma marginale Are Rich in Naturally Derived CD4+ T Lymphocyte Epitopes that Elicit Strong Recall Responses. J. Immunol. 166: 1114-1124 [Abstract] [Full Text]  
  • Barbet, A. F., Lundgren, A., Yi, J., Rurangirwa, F. R., Palmer, G. H. (2000). Antigenic Variation of Anaplasma marginale by Expression of MSP2 Mosaics. Infect. Immun. 68: 6133-6138 [Abstract] [Full Text]  
  • Rurangirwa, F. R., Stiller, D., Palmer, G. H. (2000). Strain Diversity in Major Surface Protein 2 Expression during Tick Transmission of Anaplasma marginale. Infect. Immun. 68: 3023-3027 [Abstract] [Full Text]  
  • Camacho-Nuez, M., de Lourdes Munoz, M., Suarez, C. E., McGuire, T. C., Brown, W. C., Palmer, G. H. (2000). Expression of Polymorphic msp1beta Genes during Acute Anaplasma marginale Rickettsemia. Infect. Immun. 68: 1946-1952 [Abstract] [Full Text]  
  • Tuo, W., Palmer, G. H., McGuire, T. C., Zhu, D., Brown, W. C. (2000). Interleukin-12 as an Adjuvant Promotes Immunoglobulin G and Type 1 Cytokine Recall Responses to Major Surface Protein 2 of the Ehrlichial Pathogen Anaplasma marginale. Infect. Immun. 68: 270-280 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»