OA24.06 LB
Background: The characterization of host genetic factors that allow small subsets of individuals to naturally suppress HIV-1 viral replication in the absence of antiretroviral treatment remains a priority, as an understanding of the immune mechanisms employed by these individuals to control viral replication could provide insights into potential therapeutic targets.
Methods: Therefore, in order to identify genes involved in the control of HIV-1 viral replication during chronic infection, mRNA was extracted from peripheral blood mononuclear cells isolated from 14 Black female South African HIV-1 controllers. Paired-end RNA sequencing of 100 bp fragments was performed using the HiSeq 2000 and the data obtained were processed using the GRAPE analysis pipeline. Differences in gene expression were evaluated using the R/Bioconductor package, DESeq; with genes exhibiting at least a 2-fold difference in expression and p-values of p < 0.001 considered to be differentially expressed.
Results: Genes found to be differentially expressed between the eight individuals with viral loads below 400 copies/ml and six individuals with viral loads above 400 copies/ml included several previously implicated in the control of chronic viral infections. These include LAG3, a regulator of T cell responsiveness, and genes involved in the regulation of the interferon type I antiviral response (for example IFI6, IFIT3, IFI44 and OASL). Several of the identified genes also encoded as yet functionally uncharacterized large intergenic non-coding RNAs, whose impact on HIV-1 viral control remains to be evaluated.
Conclusions: Collectively, these data describe a transcriptional signature of immune activation in chronic HIV-1 infection, which suggests the involvement of innate immune mechanisms previously shown to display substantial sex-based differences. However, whether these mechanisms directly regulate HIV-1 viral replication, or rather are activated in response to increased viral loads, remains to be established.
