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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
Primary Structural Variation in Anaplasma marginale Msp2 Efficiently Generates Immune Escape Variants.
Telmo Graça1, Lydia Paradiso2, Shira L Broschat3
1The Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, USA Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA telmo@vetmed.wsu.edu.
Anaplasma marginale evades immune responses by creating new Msp2 protein variants through segmental gene conversion. This process generates diverse Msp2 mosaics, enabling persistent infection by altering antigenic properties.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Microbial pathogens use antigenic variation to evade host immune systems, prolonging infections.
- Anaplasma marginale employs gene conversion of msp2 alleles for Msp2 variant production.
- Existing msp2 alleles are insufficient for generating the diversity needed for persistent infection.
Purpose of the Study:
- To investigate if Anaplasma marginale's segmental gene conversion generates antigenic variants.
- To determine if structural changes in Msp2 microdomains elicit a broad antibody response.
Main Methods:
- Identified Msp2 variants with structural differences in hypervariable microdomains.
- Tested whether these structural variants were recognized as distinct antigenic variants.
- Analyzed amino acid identity and structural variation in microdomains.
Main Results:
- Minimal structural differences, including single amino acid changes, were observed between Msp2 variants.
- 89% of expressed structural variants were confirmed as antigenic variants.
- Structural variation in microdomains correlated with segmental gene conversion mechanisms.
Conclusions:
- Segmental gene conversion is an effective mechanism for generating Anaplasma marginale Msp2 antigenic variants.
- These variants contribute to immune evasion and persistent infection.
- The findings highlight the role of mosaic Msp2 generation in pathogen survival.
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