Major Histocompatibility Complex-Associated Resistance to Infectious Diseases: The Case of Bovine Leukemia Virus Infection

Abstract

The major histocompatibility complex (MHC) is a polymorphic gene cluster of about 150 genes, present in all vertebrates. Many of these genes contribute to immunity. Particularly, MHC-encoded class I and class II molecules, which are typically highly polymorphic and polygenic, are central in defining the specificity of the adaptive immune response. Among the diversity of genes associated with disease resistance, MHC genes are particularly interesting as they are associated with resistance and susceptibility to a wide range of diseases, some of which produce important economic losses in livestock. Enzootic bovine leukosis is an infectious disease caused by the retrovirus bovine leukemia virus (BLV), with an important economic impact, mainly in dairy herds. In this chapter, MHC-associated genetic resistance to BLV is revised. Certain alleles of the bovine MHC (BoLA) class II locus have been found strongly associated with resistance to viral dissemination. Genetic selection of resistant animals emerges as a natural strategy for the control of infectious diseases, especially when there is no other alternative of control or prevention, as vaccines. Founded on this knowledge, a BLV control program based on selection of genetically resistant cattle was designed. The proof of concept indicates that this strategy is feasible to implement in dairy herds.

RNA Sequencing (RNA-Seq) Based Transcriptome Analysis in Immune Response of Holstein Cattle to Killed Vaccine against Bovine Viral Diarrhea Virus Type I

“…MHC is a cell surface glycoprotein molecule, having the binding ability to foreign peptides, such as viral proteins, and provides context for the recognition of T-lymphocytes responsible for cell-mediated immunity [32,33]. In studies conducted by Gutierrez et al [34] and Weigel et al [35], it was discovered that MHC genes are strongly associated with disease resistance and susceptibility to a wide range of diseases; thus, it can be a natural strategy in controlling infectious diseases, by incorporating it to the selection index and in genetic manipulation techniques.…”

Bovine leukemia virus: current perspectives

“…The coding sequence of DRA is monomorphic, while DRB3 gene is highly polymorphic. 137 The polymorphism of MHC genes was associated with resistance or susceptibility to the dissemination of the BLV in the host. Among the MHC genes studied for association with BLV phenotypes, polymorphism in exon 2 of BoLA-DRB3 was demonstrated to be stronger compared to other studied genes.…”

“…Among the MHC genes studied for association with BLV phenotypes, polymorphism in exon 2 of BoLA-DRB3 was demonstrated to be stronger compared to other studied genes. [137][138][139][140] The nomenclature of BoLA alleles is gen*allele, and two nomenclatures are used to name the different alleles of these genes. One is based on the cut pattern identified by three restriction enzymes (PCR-restriction fragment length polymorphism [RFLP] technique), which can differentiate 57 different alleles.…”

“…Thus, BoLA-DRB3*0902 allele is an excellent marker for the selection of resistant animals in the current populations 137,145,147 Its allele frequencies in different Holstein populations are relatively high (5%-15%). 143,[147][148][149][150][151][152] BoLA-DRB3*0902 animals with LPL phenotype did not transmit the infection at herd level in natural conditions, 48 and under experimental conditions, it was necessary to inoculate a large volume of blood in order to infect sheep.…”

“…145,147 Furthermore, to date, the BoLA-DRB3*0902 allele has not been associated with susceptibility to other infectious agent, nor has it negatively affected production or reproduction traits. 137,153 Moreover, R alleles are associated with resistance to intramammary infection and higher production traits. 149,150 Thus, expanding the population of cattle harboring these alleles in order to control BLV infection would additionally increase resistance to mastitis.…”