scholarly journals Antigenic Variation of Anaplasma Marginale: Major Surface Protein 2 Diversity during Cyclic Transmission between Ticks and Cattle

2001 ◽  
Vol 69 (5) ◽  
pp. 3057-3066 ◽  
Author(s):  
A. F. Barbet ◽  
Jooyoung Yi ◽  
Anna Lundgren ◽  
B. R. McEwen ◽  
E. F. Blouin ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Salivary Glands ◽  
Antigenic Variation ◽  
Hypervariable Region ◽  
Surface Protein ◽  
Genomic Expression ◽  
Major Surface Protein ◽  
Expression Site ◽  
Major Surface ◽  
Tick Salivary Glands

ABSTRACT The rickettsial pathogen Anaplasma marginale expresses a variable immunodominant outer membrane protein, major surface protein 2 (MSP2), involved in antigenic variation and long-term persistence of the organism in carrier animals. MSP2 contains a central hypervariable region of about 100 amino acids that encodes immunogenic B-cell epitopes that induce variant-specific antibodies during infection. Previously, we have shown that MSP2 is encoded on a polycistronic mRNA transcript in erythrocyte stages of A. marginale and defined the structure of the genomic expression site for this transcript. In this study, we show that the same expression site is utilized in stages of A. marginale infecting tick salivary glands. We also analyzed the variability of this genomic expression site in Oklahoma strain A. marginale transmitted from in vitro cultures to cattle and between cattle and ticks. The structure of the expression site and flanking regions was conserved except for sequence that encoded the MSP2 hypervariable region. At least three different MSP2 variants were encoded in each A. marginalepopulation. The major sequence variants did not change on passage ofA. marginale between culture, acute erythrocyte stage infections, and tick salivary glands but did change during persistent infections of cattle. The variant types found in tick salivary glands most closely resembled those present in bovine blood at the time of acquisition of infection, whether infection was acquired from an acute or from a persistent rickettsemia. These variations in structure of an expression site for a major, immunoprotective outer membrane protein have important implications for vaccine development and for obtaining an improved understanding of the mechanisms of persistence of ehrlichial infections in humans, domestic animals, and reservoir hosts.

scholarly journals Surface Protein Variation by Expression Site Switching in the Relapsing Fever Agent Borrelia hermsii

2000 ◽  
Vol 68 (12) ◽  
pp. 7114-7121 ◽  
Author(s):  
Alan G. Barbour ◽  
Carol J. Carter ◽  
Charles D. Sohaskey
Keyword(s):  
Membrane Protein ◽  
Antigenic Variation ◽  
Surface Protein ◽  
Relapsing Fever ◽  
Borrelia Hermsii ◽  
Immunodeficient Mice ◽  
Major Surface Protein ◽  
Protein Variation ◽  
Expression Site ◽  
Major Surface

ABSTRACT Borrelia hermsii, an agent of relapsing fever, undergoes antigenic variation of serotype-specifying membrane proteins during mammalian infections. When B. hermsii is cultivated in broth medium, one serotype, 33, eventually predominates in the population. Serotype 33 has also been found to be dominant in ticks but not in mammalian hosts. We investigated the biology and genetics of two independently derived clonal populations of serotype 33 of B. hermsii. Both isolates infected immunodeficient mice, but serotype 33 cells were limited in number and were only transiently present in the blood. Probes for vsp33, which encodes the serotype-specifying Vsp33 outer membrane protein, revealed that the gene was located on a 53-kb linear plasmid and that there was only one locus for the gene in serotype 33. The vsp33 probe and probes for other variable membrane protein genes showed that expression of Vsp33 was determined at the level of transcription and that when thevsp33 expression site was active, an expression site for other variable proteins was silent. The study confirmed that serotype 33 is distinct from other serotypes of B. hermsii in its biology and demonstrated that B. hermsii can change its major surface protein through switching between two expression sites.

scholarly journals Expression of Anaplasma marginale Major Surface Protein 2 Variants in Persistently Infected Ticks

2001 ◽  
Vol 69 (8) ◽  
pp. 5151-5156 ◽  
Author(s):  
José de la Fuente ◽  
Katherine M. Kocan
Keyword(s):  
Immune Response ◽  
Salivary Glands ◽  
Antigenic Variation ◽  
Surface Protein ◽  
Anaplasma Marginale ◽  
Dermacentor Variabilis ◽  
Persistently Infected ◽  
Major Surface Protein ◽  
Persistent Infections ◽  
Major Surface

ABSTRACT Anaplasma marginale, an intraerythrocytic ehrlichial pathogen of cattle, establishes persistent infections in both vertebrate (cattle) and invertebrate (tick) hosts. The ability ofA. marginale to persist in cattle has been shown to be due, in part, to major surface protein 2 (MSP2) variants which are hypothesized to emerge in response to the bovine immune response. MSP2 antigenic variation has not been studied in persistently infected ticks. In this study we analyzed MSP2 in A. marginalepopulations from the salivary glands of male Dermacentor variabilis persistently infected with A. marginaleafter feeding successively on one susceptible bovine and three sheep. New MSP2 variants appeared in each A. marginale population, and sequence alignment of the MSP2 variants revealed multiple amino acid substitutions, insertions, and deletions. These results suggest that selection pressure on MSP2 occurred in tick salivary glands independent of the bovine immune response.

scholarly journals Specific Expression of Anaplasma marginale Major Surface Protein 2 Salivary Gland Variants Occurs in the Midgut and Is an Early Event during Tick Transmission

2002 ◽  
Vol 70 (1) ◽  
pp. 114-120 ◽  
Author(s):  
Christiane V. Löhr ◽  
Fred R. Rurangirwa ◽  
Terry F. McElwain ◽  
David Stiller ◽  
Guy H. Palmer
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Surface Protein ◽  
Anaplasma Marginale ◽  
Mammalian Host ◽  
Early Event ◽  
Variant Selection ◽  
Specific Expression ◽  
Major Surface Protein ◽  
Major Surface

ABSTRACT Infectivity of Anaplasma spp. develops when infected ticks feed on a mammalian host (transmission feed). Specific Anaplasma marginale major surface protein 2 (MSP2) variants are selected for within the tick and are expressed within the salivary glands. The aims of this study were to determine when and where MSP2 variant selection occurs in the tick, how MSP2 expression is regulated in salivary glands of transmission-feeding ticks, and whether the number of A. marginale organisms per salivary gland is significantly increased during transmission feeding. The South Idaho strain of A. marginale was used, as MSP2 expression is restricted to two variants, SGV1 and SGV2, in Dermacentor andersoni. Using Western blot, real-time PCR, and DNA sequencing analyses it was shown that restriction and expression of MSP2 occurs early in the midgut within the first 48 h of the blood meal, when ticks acquire infection. A. marginale is present in the tick salivary glands before transmission feeding is initiated, but the msp2 mRNA and MSP2 protein levels per A. marginale organism increase only minimally and transiently in salivary glands of transmission-feeding ticks compared to that of unfed ticks. A. marginale numbers per tick increase gradually in salivary glands of both transmission-fed and unfed ticks. It is concluded that MSP2 variant selection is an early event in the tick and that MSP2 variants SGV1 and SGV2 are expressed both in the midgut and salivary glands. While MSP2 may be required for infectivity, there is no strict temporal correlation between MSP2 expression and the development of infectivity.

scholarly journals The polymorphic telomeres of the African trypanosome Trypanosoma brucei

2000 ◽  
Vol 28 (5) ◽  
pp. 536-540 ◽  
Author(s):  
G. Rudenko
Keyword(s):  
Trypanosoma Brucei ◽  
Surface Protein ◽  
Bloodstream Form ◽  
African Trypanosomes ◽  
African Trypanosome ◽  
Major Surface Protein ◽  
Genes Encoding ◽  
Expression Site ◽  
Major Surface

African trypanosomes have plastic genomes with extensive variability at the chromosome ends. The genes encoding the expressed major surface protein of the infective bloodstream form stages of Trypanosoma brucei and are located at telomeres. These telomeric expression-site transcription units are turning out to be surprisingly polymorphic in structure and sequence.

scholarly journals CD4+ T Lymphocytes from Anaplasma marginale Major Surface Protein 2 (MSP2) Vaccinees Recognize Naturally Processed Epitopes Conserved in MSP3

2004 ◽  
Vol 72 (6) ◽  
pp. 3688-3692 ◽  
Author(s):  
Wendy C. Brown ◽  
Guy H. Palmer ◽  
Kelly A. Brayton ◽  
Patrick F. M. Meeus ◽  
Anthony F. Barbet ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Antigenic Variation ◽  
Surface Protein ◽  
Anaplasma Marginale ◽  
Lymphocyte Response ◽  
Major Surface Protein ◽  
C Terminus ◽  
N Terminus ◽  
Major Surface

ABSTRACT Major surface protein 2 (MSP2) and MSP3 of the persistent bovine ehrlichial pathogen Anaplasma marginale are immunodominant proteins that undergo antigenic variation. The recently completed sequence of MSP3 revealed blocks of amino acids in the N and C termini that are conserved with MSP2. This study tested the hypothesis that CD4+ T cells specific for MSP2 recognize naturally processed epitopes conserved in MSP3. At least one epitope in the N terminus and two in the C terminus of MSP2 were also processed from MSP3 and presented to CD4+ T lymphocytes from MSP2-immunized cattle. This T-lymphocyte response to conserved and partially conserved epitopes may contribute to the immunodominance of MSP2 and MSP3.

scholarly journals Strain Diversity in Major Surface Protein 2 Expression during Tick Transmission of Anaplasma marginale

2000 ◽  
Vol 68 (5) ◽  
pp. 3023-3027 ◽  
Author(s):  
Fred R. Rurangirwa ◽  
David Stiller ◽  
Guy H. Palmer
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Vaccine Development ◽  
Surface Protein ◽  
Anaplasma Marginale ◽  
Major Surface Protein ◽  
Strain Diversity ◽  
Tick Transmission ◽  
Major Surface ◽  
Restricted Pattern

ABSTRACT Specific major surface protein 2 (MSP2) variants are expressed byAnaplasma marginale within the tick salivary gland and, following transmission, are expressed during acute rickettsemia. In previous work, we have shown that a restricted pattern of MSP2 variants is expressed in the salivary glands of Dermacentor andersoni ticks infected with the South Idaho strain of A. marginale. Now we demonstrate that the identical restriction does not apply to two other strains of A. marginale, and that different variants are also expressed when the same strain is transmitted by different Dermacentor spp. This indicates that antigenic diversity among strains is maintained in tick transmission and may be a significant constraint to MSP2 vaccine development.

scholarly journals Rapid Sequential Changeover of Expressed p44 Genes during the Acute Phase of Anaplasma phagocytophilum Infection in Horses

2004 ◽  
Vol 72 (12) ◽  
pp. 6852-6859 ◽  
Author(s):  
Xueqi Wang ◽  
Yasuko Rikihisa ◽  
Tzung-Hui Lai ◽  
Yumi Kumagai ◽  
Ning Zhi ◽  
...  
Keyword(s):  
Acute Phase ◽  
Anaplasma Phagocytophilum ◽  
Antigenic Variation ◽  
Hypervariable Region ◽  
Surface Protein ◽  
Intrinsic Property ◽  
Infected Horse ◽  
Major Surface ◽  
Intravenous Inoculation

ABSTRACT Anaplasma phagocytophilum immunodominant polymorphic major surface protein P44s have been hypothesized to go through antigenic variation, but the within-host dynamics of p44 expression has not been demonstrated. In the present study we investigated the composition and changes of p44 transcripts in the blood during the acute phase of well-defined laboratory A. phagocytophilum infections in naïve equine hosts. Three traveling waves of sequential population changeovers of the p44 transcript species were observed within a single peak of rickettsemia of less than 1 month. During the logarithmic increase, the rapid switch-off of the initial dominant transcript p44-18 occurred regardless of whether the bacterium was transmitted by ticks or by intravenous inoculation. Each of the subsequently dominant p44 transcript species was phylogenetically dissimilar from p44-18. Development of antibody to the hypervariable region of P44-18 during the rickettsemia suggests the suppression of dominance of immuno-cross-reactive p44 populations. When A. phagocytophilum was preincubated with plasma from the infected horse and then coincubated with HL-60 cells, the dominance of the p44-18 transcript was rapidly suppressed in vitro and most of the newly emerged p44 transcript species were previously undetected in this horse. This work provides experimental evidence of within-host p44 antigenic variation. Results suggest that the rapid and synchronized switch of expression is an intrinsic property of p44s reinitiated after transmission to naïve mammalian hosts and shaped upon exposure to immune plasma.

scholarly journals Selection for Simple Major Surface Protein 2 Variants during Anaplasma marginale Transmission to Immunologically Naïve Animals

2006 ◽  
Vol 75 (3) ◽  
pp. 1502-1506 ◽  
Author(s):  
Guy H. Palmer ◽  
James E. Futse ◽  
Christina K. Leverich ◽  
Donald P. Knowles ◽  
Fred R. Rurangirwa ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Antigenic Variation ◽  
Surface Protein ◽  
Anaplasma Marginale ◽  
Selective Advantage ◽  
Immune Selection ◽  
Animal Host ◽  
Major Surface Protein ◽  
Selection For ◽  
Major Surface

ABSTRACT Anaplasma marginale, a rickettsial pathogen, evades clearance in the animal host by antigenic variation. Under immune selection, A. marginale expresses complex major surface protein 2 mosaics, derived from multiple donor sequences. However, these mosaics have a selective advantage only in the presence of adaptive immunity and are rapidly replaced by simple variants following transmission.

scholarly journals Emergence of Anaplasma marginaleAntigenic Variants during Persistent Rickettsemia

1999 ◽  
Vol 67 (11) ◽  
pp. 5834-5840 ◽  
Author(s):  
Dorothy M. French ◽  
Wendy C. Brown ◽  
Guy H. Palmer
Keyword(s):  
Antigenic Variation ◽  
Hypervariable Region ◽  
Surface Protein ◽  
Antibody Responses ◽  
Structural Variants ◽  
Granulocytic Ehrlichiosis ◽  
Cowdria Ruminantium ◽  
Hypervariable Regions ◽  
Human Granulocytic Ehrlichiosis ◽  
Major Surface

ABSTRACT 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 expressedA. 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 ofA. marginale persistence.

scholarly journals Diversity and complexity of the large surface protein family in the compacted genomes of various Pneumocystis species

2019 ◽  
Author(s):  
Liang Ma ◽  
Zehua Chen ◽  
Da Wei Huang ◽  
Ousmane H. Cissé ◽  
Jamie L. Rothenburger ◽  
...  
Keyword(s):  
Antigenic Variation ◽  
Life Stage ◽  
Surface Protein ◽  
Opportunistic Pathogen ◽  
Surface Proteins ◽  
Surface Glycoprotein ◽  
Mammalian Host ◽  
Expression Site ◽  
Phylogeny And Evolution ◽  
Major Surface

AbstractPneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multi-copy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneumocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins, and provide detailed description of the classification, unique characteristics and phylogenetic relatedness of five Msg families. We further describe the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. carinii from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests a wide variety of functions for this superfamily, not only conferring antigenic variation to allow immune evasion but also mediating life-stage development, optimizing cell mobility and adhesion, and adapting to specific host niches or environmental conditions. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology.

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