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



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.



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.



Data from this study suggest an involvement for the OAS gene family in the control of HIV-1 infection.
Department of Biomedical and Biotechnological Sciences, University of Catania, Italy.
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P
Fagone
Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Garibaldi Nesima Hospital, University of Catania, Catania, Italy.
G
G
Nunnari
Department of Biomedical and Biotechnological Sciences, University of Catania, Italy.
F
F
Lazzara
Department of Biomedical and Biotechnological Sciences, University of Catania, Italy.
A
A
Longo
Department of Biomedical and Biotechnological Sciences, University of Catania, Italy.
D
D
Cambria
Department of Biomedical and Biotechnological Sciences, University of Catania, Italy.
G
G
Distefano
Department of Biomedical and Biotechnological Sciences, University of Catania, Italy.
M
M
Palumbo
Department of Biomedical and Biotechnological Sciences, University of Catania, Italy.
F
F
Nicoletti
Department of Biomedical and Biotechnological Sciences, University of Catania, Italy.
L
L
Malaguarnera
Department of Biomedical and Biotechnological Sciences, University of Catania, Italy. Electronic address: mdirosa@unict.it.
M
M
Di Rosa
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D018791:CD4 Lymphocyte Count; D019295:Computational Biology; D053263:Gene Regulatory Networks; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D046228:Microarray Analysis; D009000:Monocytes / Q000378:metabolism / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction; D019562:Viral Load
C475085:OAS1 protein, human; C000607948:OAS2 protein, human; C115020:OASL protein, human; D015088:2',5'-Oligoadenylate Synthetase; C577439:OAS3 protein, human
HIV-1; Monocyte; OAS1; OAS2; OAS3; OASL