Induction of OAS gene family in HIV monocyte infected patients with high and low viral load

- The OAS gene family is significantly upregulated in monocyte of HIV-1 patients with HVL and LVL.
- The IFN Type 1 and 2 modulate significantly the OAS gene expression.
- The expression of OAS genes inversely correlate to CD4 count in HIV-1 patients.
- OAS genes are sensitive to viral load in the monocytes of HIV-1 patients.

BackgroundThe innate immunity plays a predominant role in the early control of HIV infection, before the induction of adaptive immune responses. The cytokine secretion operated by the CD4+ T helper cells is able to induce a response in the innate immunity cells and significantly affect HIV-1 persistence and replication. One of the pathways activated by monocytes to restrain viral infection is the 2′ -5′ -oligoadenylate synthetase (OAS)/RNase L pathway. OAS is activated by dsRNA and IFNs to produce 2′ -5′ oligoadenylates, which are activators of RNase L. This enzyme degrades viral and cellular RNAs, thus restricting viral infection.Materials and methodsWe analyzed a microarray dataset obtained from the NCBI Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) databank (accession number GSE18464) in order to verify the modulation of the OAS gene family in CD14 + monocytes isolated from 55 subjects, 22 with HIV-1 HVL (high viral load), and 22 with HIV-1 LVL (low viral load), as well as in 11 HIV-1 seronegative controls. We have validated the data on the expression levels of the OAS genes by performing real-time PCR on monocyte from a cohort of HIV infected patients (n = 20), with clinical characteristics similar to those of the patients recruited in the study present in the microarray.ResultsMicroarray analysis showed that OAS gene family are significantly upregulated in monocyte of HIV-1 patients with HVL, as compared to LVL patients and to healthy donors. Furthermore, we showed a significant correlation between the OAS gene family and the log2 viral load and CD4 count. These results were confirmed by the in vitro validation.ConclusionsData from this study suggest an involvement for the OAS gene family in the control of HIV-1 infection.