|Title||Association of a single nucleotide polymorphism in ubxn6 gene with long term non progression phenotype in hiv-positive individuals.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Díez-Fuertes, F, de la Torre-Tarazona, HErick, Calonge, E, Pernas, M, Bermejo, M, García-Pérez, J, Álvarez, A, Capa, L, Garcia-Garcia, F, Saumoy, M, Riera, M, Boland-Auge, A, López-Galíndez, C, Lathrop, M, Dopazo, J, Sakuntabhai, A, Alcamí, J|
|Journal||Clin Microbiol Infect|
|Date Published||2019 May 31|
OBJECTIVES: The long-term non-progressors (LTNP) are a heterogeneous group of HIV-positive individuals characterized by their ability to maintain high CD4 T-cell counts and partially control viral replication for years in the absence of antiretroviral therapy. The present study aims to identify host single nucleotide polymorphisms (SNPs) associated with non-progression in a cohort of 352 individuals.METHODS: DNA microarrays and exome sequencing were used for genotyping about 240,000 functional polymorphisms throughout more than 20,000 human genes. The allele frequencies of 85 LTNPs were compared with a control population. SNPs associated with LTNPs were confirmed in a population of typical progressors. Functional analyses in the affected gene were carried out through knockdown experiments in HeLa-P4, macrophages and dendritic cells.RESULTS: Several SNPs located within the MHC region previously related to LTNPs were confirmed in this new cohort. The SNP rs1127888 (UBXN6) surpassed the statistical significance of these markers after Bonferroni correction (q=2.11x10). An uncommon allelic frequency of rs1127888 among LTNPs was confirmed by comparison with typical progressors and other publicly available populations. UBXN6-knockdown experiments caused an increase of CAV1 expression and its accumulation in the plasma membrane of different cell types. In vitro infection of these cells with HIV-1 replication-competent recombinant viruses caused a reduction of the viral replication capacity compared with their corresponding wild type cells expressing UBXN6.CONCLUSIONS: A higher prevalence of Ala31Thr in UBXN6 was found among LTNPs within its N-terminal region, which is crucial for UBXN6/VCP protein complex formation. UBXN6-knockdown affected CAV1 turnover and HIV-1 replication capacity.
|Alternate Journal||Clin. Microbiol. Infect.|