Disease relevance of msp2

• In Anaplasma marginale pseudogenes for two antigenically variable gene families, msp2 and msp3, appear in concert [1].
• The msp2 gene in the A. phagocytophilum strain HZ genome was a single-copy gene and was located downstream of two Ehrlichia chaffeensis omp-1 homologs and a decarboxylase gene (ubiD) [2].
• However, the transcript of the msp2 gene was undetectable in A. phagocytophilum strain HZ in SCID mice and Ixodes scapularis ticks infected with strain NTN-1 [2].
• This finding supports the hypothesis that the occurrence of superinfection reflects the differences in the msp2 repertoire and corresponding diversity of variants [3].
• The simultaneous clearance of variants of the two most immunodominant surface proteins of A. marginale followed by emergence of unique variants indicates that the switch rates and immune selection for MSP2 and MSP3 are sufficiently similar to explain the cyclic bacteremia observed during infection in the immunocompetent host [4].

High impact information on msp2

• The genome contains unusual functional pseudogenes that belong to the msp2 superfamily and play an integral role in surface coat antigenic variation, and are thus distinctly different from pseudogenes described as byproducts of reductive evolution in other Rickettsiales [5].
• This indicates that the msp2 expressed by organisms within the tick salivary gland predicts the variant type responsible for acute rickettsemia and disease [6].
• These results suggest that loss of memory T cell responses following A. marginale infection is due to a mechanism other than induction of T regulatory cells, such as peripheral deletion of MSP2-specific T cells [7].
• During A. marginale infection, dynamic and extensive amino acid sequence variation in MSP2 occurs through recombination of msp2 pseudogenes into the msp2 expression site, followed by sequential segmental gene conversions to generate additional variants [8].
• Antigenic variation of Anaplasma marginale msp2 occurs by combinatorial gene conversion [9].

Biological context of msp2

• Five strains of A. marginale were selected in order to identify and compare msp2 pseudogene content; these included strains with similar and different msp1alpha genotypes, and genotypes that were representative of the strains that were found in the superinfected animals [3].
• Characterization of the Anaplasma marginale msp2 locus and its synteny with the omp1/p30 loci of Ehrlichia chaffeensis and E. canis [10].
• Comparison of amino acid sequences encoded by A. centrale msp-2 transcripts from the initial postimmunization period and from sequential time points during persistence of the vaccine strain revealed a central hypervariable domain flanked by conserved amino and carboxy-terminal regions [11].
• The immunoprotective Anaplasma marginale major surface protein 2 is encoded by a polymorphic multigene family [12].
• Pulsed-field gel electrophoresis and Southern blot analysis revealed the presence of multiple msp-2 gene copies that were widely distributed throughout the chromosomes of all three strains examined [12].

Anatomical context of msp2

• 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 [13].
• Numerous CD4(+) T cell epitopes in the hypervariable and conserved regions of MSP2 contribute to this immunodominance [7].
• 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 [14].
• As gammadelta T cells proliferate in A. marginale-stimulated lymphocyte cultures, this study hypothesized that gammadelta T cells respond to the abundant, immunodominant MSP2 [15].
• This conservation of both genomic structure for generating MSP-2 variants and the CD4(+)-T-cell epitopes between these two genetically distinct Anaplasma species indicates that they present a similar repertoire of MSP-2 epitopes to the immune system and that this similarity may be responsible for all or part of the A. centrale vaccine efficacy [11].

Other interactions of msp2

• Interestingly, the 5' structure of this A. marginale msp2 locus is conserved in the omp1 gene locus of Ehrlichia chaffeensis and p30 gene locus of E. canis despite marked divergence between genera in the structure of the 3' region of the loci [10].

Analytical, diagnostic and therapeutic context of msp2

• In this manuscript, we used sequence analysis of msp2 transcripts to show that a restricted repertoire of variant types, designated SGV1 and SGV2, is expressed within the tick salivary gland [6].
• Southern blot analysis of strains associated with superinfection revealed distinctly different msp2 banding patterns, in contrast to a pattern suggesting identical pseudogene content among related strains not associated with superinfection [3].
• By using a quantitative competitive PCR to identify rickettsemic cycles, msp-2 transcripts expressed in vivo were isolated from peak rickettsemia of sequential cycles [16].
• Two-color immunofluorescence using variant-specific antibody showed that emergence of MSP-2 variants resulted in expression of a minimum of three antigenic types of MSP-2 within one rickettsemic cycle [16].
• New MSP2 variants appeared in each A. marginale population, and sequence alignment of the MSP2 variants revealed multiple amino acid substitutions, insertions, and deletions [17].

References