|
Basic Characteristics of Mutations
|
|
Mutation Site
|
D30N |
|
Mutation Site Sentence
|
Figure 1 Permissiveness and non-permissiveness heatmaps of published RAMs/HLA alleles combinations. Log-transformed fold changes in binding are color-coded. Red indicates non-permissiveness, green permissiveness, and grey neutrality. Since the peptides included in this figure are based on predicted binding (as listed on the Los Alamos HIV Immunology Database), all fold changes are represented, regardless of high-binding categorization. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
PR |
|
Standardized Encoding Gene
|
gag-pol
|
|
Genotype/Subtype
|
HIV-1 B |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HIV Infections
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
PIs |
|
Location
|
US;European;South African |
|
Literature Information
|
|
PMID
|
40137693
|
|
Title
|
Computational and Population-Based HLA Permissiveness to HIV Drug Resistance-Associated Mutations
|
|
Author
|
Mahmud R,Krullaars Z,van Osch J,Rickett D,Brumme ZL,Hensley KS,Rokx C,Gruters RA,van Kampen JJA,Mesplede T
|
|
Journal
|
Pathogens (Basel, Switzerland)
|
|
Journal Info
|
2025 Feb 20;14(3):207
|
|
Abstract
|
The presentation of HIV peptides by the human leukocyte antigen (HLA) complex to CD8+ cytotoxic T-cells (CTLs) is critical to limit viral pathogenesis. HIV can mutate to evade HLA-restricted CTL responses and resist antiretroviral drugs, raising questions about how it balances these evolutionary pressures. Here, we used a computational approach to assess how drug resistance-associated mutations (RAMs) affect the binding of HIV-1 subtype B or C peptides to the most prevalent HLA alleles in US, European, and South African populations. We predict RAMs that may be favored in certain populations and report the under-representation of Y181C in people expressing HLA-B*57:01. This finding agreed with our computational predictions when Y181C was at the major anchor site P2, suggesting the potential relevance of our approach. Overall, our findings lay out a conceptual framework to study the implications of HLA alleles on the emergence of HIV RAMs at the individual and population levels.
|
|
Sequence Data
|
-
|