Polymorphisms located within the MHC have been linked to many disease outcomes by mechanisms not yet fully understood in most cases. Variants located within untranslated regions of HLA genes are involved in allele specific expression and may therefore underlie some of these disease associations. We determined sequences extending nearly 2kb upstream of the transcription start site for 68 alleles from 57 major lineages of classical HLA class I genes. The nucleotide diversity within this promoter segment roughly follows that seen within the coding regions, with HLA-B showing the highest (~1.9%), followed by HLA–A (~1.8%), and HLA–C showing the lowest diversity (~0.9%). In spite of its greater diversity, HLA-B mRNA expression levels determined in 178 European Americans do not vary in an allele- or lineage-specific manner, unlike the differential expression levels of HLA-A or HLA-C reported previously. Close proximity of promoter sequences in phylogenetic trees is roughly reflected by similarity of expression pattern for most HLA-A and -C loci. While promoter sequence divergence might impact promoter activity, we observed no clear link between the phylogenetic structure as represented by pairwise nucleotide differences in the promoter regions with estimated differences in mRNA expression levels for the classical class I loci. Further, no pair of class I loci showed coordinated expression levels, suggesting that distinct mechanisms across loci determine their expression level under non-stimulated conditions. These data serve as a foundation for more in depth analysis of the functional consequences of promoter region variation within the classical HLA class I loci.

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This study set out to determine the frequency of antiretroviral drug resistance mutations in treatment-naive subjects of the north central Mexican state of San Luis Potosí. Mexican studies of antiretroviral drug resistance mutations have focused mainly on large metropolitan areas and border towns subjected to intense international migrations. This study set forth to describe the frequency of these mutations in a Mexican region less subjected to such migratory influences and more representative of smaller Mexican cities. Thirty-eight full-length pol sequences spanning the protease, reverse-transcriptase, and integrase-encoding regions were obtained from 42 treatment-naive human immunodeficiency virus (HIV)-infected subjects. Most exhibited subtype B homology, but CRF02_AG was also detected. Evidence of APOBEC3 hypermutation was seen in two samples. Calibrated population analysis revealed a surveillance drug resistance mutation prevalence of 4.9% for protease inhibitors, of 2.7% for nucleoside reverse transcriptase inhibitors, of 8.1% for non-nucleoside reverse transcriptase inhibitors, and an overall prevalence of 9.5%. This corresponds to an intermediate level of transmitted drug resistance according to the World Health Organization. The identification of integrase mutations suggests that transmitted drug mutations are being imported, as inhibitors targeting integrase have not been widely used in Mexico. Our results provide a greater understanding of HIV diversity in Mexico and highlight the way internal migrations allow HIV mutations and genetic features to permeate regions less subjected to international migrations. The implications of these findings will become more evident as Mexico hosts increased repatriations of migrants in the coming years.