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

Background: The 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 methods: We 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. Results: Microarray 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. Conclusions: Data from this study suggest an involvement for the OAS gene family in the control of HIV-1 infection.