Phenotypic Selection of Dairy Cattle Infected with Bovine Leukemia Virus Demonstrates Immunogenetic Resilience through NGS-Based Genotyping of BoLA MHC Class II Genes

Characterization of the bovine leukocyte antigen (BoLA) DRB3 gene has shown that specific alleles associate with susceptibility or resilience to the progression of bovine leukemia virus (BLV), measured by proviral load (PVL). Through surveillance of multi-farm BLV eradication field trials, we observ...

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Main Authors: Chaelynne E. Lohr, Kelly R. B. Sporer, Kelsey A. Brigham, Laura A. Pavliscak, Matelyn M. Mason, Andrew Borgman, Vickie J. Ruggiero, Tasia M. Taxis, Paul C. Bartlett, Casey J. Droscha
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/11/1/104
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author Chaelynne E. Lohr
Kelly R. B. Sporer
Kelsey A. Brigham
Laura A. Pavliscak
Matelyn M. Mason
Andrew Borgman
Vickie J. Ruggiero
Tasia M. Taxis
Paul C. Bartlett
Casey J. Droscha
author_facet Chaelynne E. Lohr
Kelly R. B. Sporer
Kelsey A. Brigham
Laura A. Pavliscak
Matelyn M. Mason
Andrew Borgman
Vickie J. Ruggiero
Tasia M. Taxis
Paul C. Bartlett
Casey J. Droscha
author_sort Chaelynne E. Lohr
collection DOAJ
description Characterization of the bovine leukocyte antigen (BoLA) DRB3 gene has shown that specific alleles associate with susceptibility or resilience to the progression of bovine leukemia virus (BLV), measured by proviral load (PVL). Through surveillance of multi-farm BLV eradication field trials, we observed differential phenotypes within seropositive cows that persist from months to years. We sought to develop a multiplex next-generation sequencing workflow (NGS-SBT) capable of genotyping 384 samples per run to assess the relationship between BLV phenotype and two BoLA genes. We utilized longitudinal results from milk ELISA screening and subsequent blood collections on seropositive cows for PVL determination using a novel BLV proviral load multiplex qPCR assay to phenotype the cows. Repeated diagnostic observations defined two distinct phenotypes in our study population, ELISA-positive cows that do not harbor detectable levels of provirus and those who do have persistent proviral loads. In total, 565 cows from nine Midwest dairy farms were selected for NGS-SBT, with 558 cows: 168 BLV susceptible (ELISA-positive/PVL-positive) and 390 BLV resilient (ELISA-positive/PVL-negative) successfully genotyped. Three BoLA-DRB3 alleles, including one novel allele, were shown to associate with disease resilience, <i>*009:02</i>, <i>*044:01</i>, and <i>*048:02</i> were found at rates of 97.5%, 86.5%, and 90.3%, respectively, within the phenotypically resilient population. Alternatively, <i>DRB3*015:01</i> and <i>*027:03</i>, both known to associate with disease progression, were found at rates of 81.1% and 92.3%, respectively, within the susceptible population. This study helps solidify the immunogenetic relationship between BoLA-DRB3 alleles and BLV infection status of these two phenotypic groupings of US dairy cattle.
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spelling doaj.art-933d472ec6584a87bf1f46d21eba8a182023-11-23T15:00:26ZengMDPI AGPathogens2076-08172022-01-0111110410.3390/pathogens11010104Phenotypic Selection of Dairy Cattle Infected with Bovine Leukemia Virus Demonstrates Immunogenetic Resilience through NGS-Based Genotyping of BoLA MHC Class II GenesChaelynne E. Lohr0Kelly R. B. Sporer1Kelsey A. Brigham2Laura A. Pavliscak3Matelyn M. Mason4Andrew Borgman5Vickie J. Ruggiero6Tasia M. Taxis7Paul C. Bartlett8Casey J. Droscha9CentralStar Cooperative, Lansing, MI 48910, USACentralStar Cooperative, Lansing, MI 48910, USACentralStar Cooperative, Lansing, MI 48910, USACentralStar Cooperative, Lansing, MI 48910, USACentralStar Cooperative, Lansing, MI 48910, USABorgman Consulting Group LLC, Alma, MI 48801, USACollege of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USADepartment of Animal Science, College of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USACollege of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USACentralStar Cooperative, Lansing, MI 48910, USACharacterization of the bovine leukocyte antigen (BoLA) DRB3 gene has shown that specific alleles associate with susceptibility or resilience to the progression of bovine leukemia virus (BLV), measured by proviral load (PVL). Through surveillance of multi-farm BLV eradication field trials, we observed differential phenotypes within seropositive cows that persist from months to years. We sought to develop a multiplex next-generation sequencing workflow (NGS-SBT) capable of genotyping 384 samples per run to assess the relationship between BLV phenotype and two BoLA genes. We utilized longitudinal results from milk ELISA screening and subsequent blood collections on seropositive cows for PVL determination using a novel BLV proviral load multiplex qPCR assay to phenotype the cows. Repeated diagnostic observations defined two distinct phenotypes in our study population, ELISA-positive cows that do not harbor detectable levels of provirus and those who do have persistent proviral loads. In total, 565 cows from nine Midwest dairy farms were selected for NGS-SBT, with 558 cows: 168 BLV susceptible (ELISA-positive/PVL-positive) and 390 BLV resilient (ELISA-positive/PVL-negative) successfully genotyped. Three BoLA-DRB3 alleles, including one novel allele, were shown to associate with disease resilience, <i>*009:02</i>, <i>*044:01</i>, and <i>*048:02</i> were found at rates of 97.5%, 86.5%, and 90.3%, respectively, within the phenotypically resilient population. Alternatively, <i>DRB3*015:01</i> and <i>*027:03</i>, both known to associate with disease progression, were found at rates of 81.1% and 92.3%, respectively, within the susceptible population. This study helps solidify the immunogenetic relationship between BoLA-DRB3 alleles and BLV infection status of these two phenotypic groupings of US dairy cattle.https://www.mdpi.com/2076-0817/11/1/104bovine leukemia virusELISAproviral loadBoLAMHC Class IIsequence-based typing
spellingShingle Chaelynne E. Lohr
Kelly R. B. Sporer
Kelsey A. Brigham
Laura A. Pavliscak
Matelyn M. Mason
Andrew Borgman
Vickie J. Ruggiero
Tasia M. Taxis
Paul C. Bartlett
Casey J. Droscha
Phenotypic Selection of Dairy Cattle Infected with Bovine Leukemia Virus Demonstrates Immunogenetic Resilience through NGS-Based Genotyping of BoLA MHC Class II Genes
Pathogens
bovine leukemia virus
ELISA
proviral load
BoLA
MHC Class II
sequence-based typing
title Phenotypic Selection of Dairy Cattle Infected with Bovine Leukemia Virus Demonstrates Immunogenetic Resilience through NGS-Based Genotyping of BoLA MHC Class II Genes
title_full Phenotypic Selection of Dairy Cattle Infected with Bovine Leukemia Virus Demonstrates Immunogenetic Resilience through NGS-Based Genotyping of BoLA MHC Class II Genes
title_fullStr Phenotypic Selection of Dairy Cattle Infected with Bovine Leukemia Virus Demonstrates Immunogenetic Resilience through NGS-Based Genotyping of BoLA MHC Class II Genes
title_full_unstemmed Phenotypic Selection of Dairy Cattle Infected with Bovine Leukemia Virus Demonstrates Immunogenetic Resilience through NGS-Based Genotyping of BoLA MHC Class II Genes
title_short Phenotypic Selection of Dairy Cattle Infected with Bovine Leukemia Virus Demonstrates Immunogenetic Resilience through NGS-Based Genotyping of BoLA MHC Class II Genes
title_sort phenotypic selection of dairy cattle infected with bovine leukemia virus demonstrates immunogenetic resilience through ngs based genotyping of bola mhc class ii genes
topic bovine leukemia virus
ELISA
proviral load
BoLA
MHC Class II
sequence-based typing
url https://www.mdpi.com/2076-0817/11/1/104
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