Several single nucleotide polymorphisms (SNPs) located within the major histocompatibility complex (MHC) region related to the long-term non-progressors phenotype were confirmed in study results published in Clinical Microbiology and Infection.

Long term non-progressors comprise a heterogenous group of individuals with HIV characterized by their ability to maintain high levels of CD4+ T-cell counts and control viral replication for extended periods without antiretroviral therapy. The allele frequencies of 85 long term non-progressors were compared with control populations. In both groups, DNA microarrays and exome sequencing were used to genotype approximately 240,000 functional polymorphisms throughout more than 20,000 human genes.

This analysis confirmed several SNPs within the MHC region previously related to long term non-progressors and found that the SNP rs1127888 located in the UBXN6 gene surpassed the statistical significance of these markers after Bonferroni correction (q=2.11×10-6). Further, functional analyses silencing UBXN6 were preformed to clarify their role in HIV immunopathogenesis. UBXN6 silencing resulted in changes to CAV1 expression. CAV1 is an essential protein in the organization of lipid rafts and caveolae that binds with HIV and penetrates plasma membranes.

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According to the investigators, the main discovery of this study was “the association of rs1127888-T located in UBXN6 with [long term non-progressor] phenotype along with the role of this gene regulating CAV1 availability within cells and affecting HIV-1 replication capacity.” It appears that accumulation of CAV1 in the plasma membrane restricts virus infection by mechanisms that require further investigation.


Díez-Fuertes F, Erick de la Torre-Tarazona H, Calonge E, et al. Association of a single nucleotide polymorphism in ubxn6 gene with long term non progression phenotype in hiv-positive individuals [published online May 31 2019]. Clin Microbiol Infect. doi:10.1016/j.cmi.2019.05.015