Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.
The process of specialty choice can be described usefully as a socially constructed process of "trying on possible selves" (i.e., projecting oneself into hypothetical career and personal roles). This may explain role models' exceptional influence in disproving negative stereotypes. Medical students' choices can best be facilitated by recognizing their needs to gain knowledge not only about specialty content, but also about practitioners' lives and the students' own present and possible selves.
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