Increased Prevalence of Unstable HLA-C Variants in HIV-1 Rapid-Progressor Patients.
Chiara StefaniAntonella SangalliElena LocatelliTania FedericoGiovanni MalerbaMaria Grazia RomanelliGustavo Adolfo ArgañarazBosco Christiano Maciel Da SilvaAlberto Jose Duarte Da SilvaJorge Simão do Rosário CassebEnrique Roberto ArgañarazAlessandra RuggieroDonato ZipetoPublished in: International journal of molecular sciences (2022)
HIV-1 infection in the absence of treatment results in progression toward AIDS. Host genetic factors play a role in HIV-1 pathogenesis, but complete knowledge is not yet available. Since less-expressed HLA-C variants are associated with poor HIV-1 control and unstable HLA-C variants are associated with higher HIV-1 infectivity, we investigated whether there was a correlation between the different stages of HIV-1 progression and the presence of specific HLA-C allotypes. HLA-C genotyping was performed using allele-specific PCR by analyzing a treatment-naïve cohort of 96 HIV-1-infected patients from multicentric cohorts in the USA, Canada, and Brazil. HIV-1-positive subjects were classified according to their different disease progression status as progressors (Ps, n = 48), long-term non-progressors (LTNPs, n = 37), and elite controllers (ECs, n = 11). HLA-C variants were classified as stable or unstable according to their binding stability to β2-microglobulin/peptide complex. Our results showed a significant correlation between rapid progression to AIDS and the presence of two or one unstable HLA-C variants ( p -value: 0.0078, p -value: 0.0143, respectively). These findings strongly suggest a link between unstable HLA-C variants both at genotype and at allele levels and rapid progression to AIDS. This work provides further insights into the impact of host genetic factors on AIDS progression.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected patients
- hiv infected
- human immunodeficiency virus
- copy number
- hiv aids
- men who have sex with men
- genome wide
- end stage renal disease
- chronic kidney disease
- south africa
- healthcare
- hepatitis c virus
- high throughput
- risk factors
- dna methylation
- gene expression
- ejection fraction
- patient reported outcomes
- transcription factor
- high resolution
- high speed
- dna binding
- atomic force microscopy