Adaptation of HIV-1 to human leukocyte antigen class I

Abstract

The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host–pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8+ T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection1. Mutation within these epitopes can allow viral escape from CD8+ T-cell recognition. Here we analysed viral sequences and HLA alleles from >2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128–135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8+ T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.

Host-Specific Adaptation of HIV-1 Subtype B in the Japanese Population

“…By extension, HIV sequences circulating in a given host population exhibit polymorphisms that reflect the HLA allele distribution of that population (9). Because HLA class I allele distributions differ among racial and ethnic groups worldwide (10), the pattern and diversity of HLA-associated escape mutations are also likely to be somewhat distinct to each race and region.…”

Tug-of-war between driver and passenger mutations in cancer and other adaptive processes

“…Examples include viral adaptation during infection (1), the emergence of antibiotic resistance (2), artificial selection in biotechnology (3), and cancer (4). Rapid adaptation is characterized by three key features: (i) the availability of strongly advantageous traits accessible by rare mutations, (ii) an elevated mutation rate (1), and (iii) a dynamic population size (5). Because traditional theories of gradual adaptation are not applicable under these conditions, new approaches are needed.…”

Ebolavirus evolves in human to minimize the detection by immune cells by accumulating adaptive mutations

“…Taken together, our results showed that EBOV does not appear to be under diversifying selection pressure, but under purifying selection that appears to be the driving force on their protein coding genes. Results provided an alternative perspective than the current prevailing hypothesis that genes encoding antigens can be highly variable to evade host immunity [5,9,16]. Moreover, the synonymous nucleotide changes could also exert modifications to the secondary structure of regulatory cis-RNA sequences.…”