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espanolEl complejo principal de histocompatibilidad o MHC (denominado en la especie bovina “antigeno leucocitario bovino, BoLA”) esta compuesto por un gran numero de genes involucrados en la respuesta inmune dentro de una misma region cromosomica. Muchos de estos genes presentan niveles extraordinarios de polimorfismo. Ademas, estos loci han sido asociados a enfermedades infecciosas, autoinmunes y a caracteres productivos en diferentes especies de mamiferos. Es por esta razon, que el estudio de su estructura, polimorfismo y evolucion ha sido de gran interes para biologos, genetistas y veterinarios durante las ultimas decadas. El objetivo de la presente revision consiste en analizar el estado del arte sobre la caracterizacion de la diversidad genetica de los loci del BoLA, con especial enfasis en el gen BoLA-DRB3 en las razas bovinas criollas americanas. En este sentido, se detallan las metodologias utilizadas para el genotipado de este gen (serologicas y moleculares). Ademas, se describen los principales resultados obtenidos a partir del estudio de la diversidad genetica del gen BoLA-DRB3, asi como de los estudios de asociacion de este locus con enfermedades infecciosas en bovinos criollos americanos. Aunque mucho se ha avanzado en el conocimiento de la diversidad genetica del gen BoLA-DRB3, aun existe un largo camino por recorrer. EnglishThe major histocompatibility complex or MHC (called in the bovine species "bovine leukocyte antigen,BoLA") is composed of a large number of genes involved in the immune response within the same chromosomalregion. Many of these genes have extraordinary levels of polymorphism. Furthermore, these loci have beenassociated with infectious and autoimmune diseases and with productive traits in different mammalian species. It isfor this reason that the study of its structure, polymorphismand evolution has been of great interest to biologists,geneticists and veterinarians during the last decades. The objective of this review is to analyze the state of the art onthe characterizationof the genetic diversity of BoLAloci, withspecial emphasis onthe BoLADRB3 gene inAmerican Creole bovine breeds. In this sense, the methodologies used for the genotyping of this gene (serologicaland molecular) are detailed. In addition, the main results obtained fromthe study of the genetic diversity of theBoLADRB3 gene are described, as well as fromthe association studies of this locus with infectious diseases inAmerican Creole cattle. Although much progress has been made in understanding the genetic diversity of the BoLADRB3 gene, there is still a long way to go.

The genetic diversity of the BoLA-DRB3 gene has been reported in different cattle breeds owing to its central role in the immune response. However, it is still unknown in hundreds of cattle breeds, especially native populations. Here, we studied BoLA-DRB3 genetic diversity in Highland Creole cattle (CrAl) from Western Bolivia, raised at altitudes between 3800 and 4200 m. DNAs from 48 CrAl cattle were genotyped for BoLA-DRB3 exon 2 alleles using polymerase chain reaction-sequence-based typing (PCR-SBT). The results were compared with 1341 previously reported data from Tropical Creole cattle and other breeds raised in the region. Twenty-three BoLA-DRB3 alleles were identified in CrAl, including the BoLA-DRB3*029:02 variant previously detected in other Creole cattle. Observed and expected heterozygosity were 0.87 and 0.93, respectively. Nucleotide diversity and the number of pairwise difference values were 0.078 and 19.46, respectively. The average number of nonsynonymous and synonymous substitutions were 0.037 and 0.097 for the entire BoLA-DRB3 exon 2, and 0.129 and 0.388 for the antigen-binding site, respectively. Venn analysis and the review of the IPD-MHC database and the literature showed that 2 of 64 alleles were only detected in CrAl, including BoLA-DRB3*029:01 previously reported in African cattle and *048:01 detected in Philippine cattle. Two additional alleles, BoLA-DRB3*007:02 and *029:02, were only present in CrAl and Lowland Creole cattle. Principal Component Analysis (PCA) showed that Bolivian Creole cattle breeds were closely located but they were distant from the Colombian Harton del Valle Creole. FST analysis showed a low degree of genetic differentiation between Highland and Lowland Bolivian Creole cattle (FST = 0.015). The present results contribute to increasing our knowledge of BoLA-DRB3 genetic diversity in cattle breeds.

The genus Flavivirus includes a range of mosquito-specific viruses in addition to well-known medically important arboviruses. Isolation and comprehensive genomic analyses of viruses in mosquitoes collected in Bolivia resulted in the identification of three novel flavivirus species. Psorophora flavivirus (PSFV) was isolated from Psorophora albigenu. The coding sequence of the PSFV polyprotein shares 60 % identity with that of the Aedes-associated lineage II insect-specific flavivirus (ISF), Marisma virus. Isolated PSFV replicates in both Aedes albopictus- and Aedes aegypti-derived cells, but not in mammalian Vero or BHK-21 cell lines. Two other flaviviruses, Ochlerotatus scapularis flavivirus (OSFV) and Mansonia flavivirus (MAFV), which were identified from Ochlerotatus scapularis and Mansonia titillans, respectively, group with the classical lineage I ISFs. The protein coding sequences of these viruses share only 60 and 40 % identity with the most closely related of known lineage I ISFs, including Xishuangbanna aedes flavivirus and Sabethes flavivirus, respectively. Phylogenetic analysis suggests that MAFV is clearly distinct from the groups of the current known Culicinae-associated lineage I ISFs. Interestingly, the predicted amino acid sequence of the MAFV capsid protein is approximately two times longer than that of any of the other known flaviviruses. Our results indicate that flaviviruses with distinct features can be found at the edge of the Bolivian Amazon basin at sites that are also home to dense populations of human-biting mosquitoes.