C Sanfilippo1, D Cambria1, A Longo1, M Palumbo1, R Avola1, M Pinzone2, G Nunnari3, F Condorelli4, G Musumeci5, R Imbesi5, P Castogiovanni5, L Malaguarnera1, Michelino Di Rosa6,7. 1. Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy. 2. Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, USA. 3. Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. 4. Department of Pharmacological Sciences, Università del Piemonte Orientale "A. Avogadro", 28100, Novara, Italy. 5. Human Anatomy and Histology Section, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy. 6. Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy. mdirosa@unict.it. 7. Human Anatomy and Histology Section, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy. mdirosa@unict.it.
Abstract
OBJECTIVE: The HIV-1 virus activates the complement system, an essential element of the immune system. SERPING1 is a protease inhibitor that disables C1r/C1s in the C1 complex of the classical complement pathway. METHODS: In this paper, we performed an analysis of several microarrays deposited in GEO dataset to demonstrate that SERPING1 mRNA is modulated in CD14+ monocytes from HIV-1-infected individuals. In addition, data were validated on monocytes isolated from seronegative healthy volunteers, treated with IFNs. RESULTS: Our analysis shows that SERPING1 mRNA is overexpressed in monocytes from HIV-1+ patients and the expression levels correlate positively with viral load and negatively with the CD4+ T-cell count. Of note, anti-retroviral therapy is able to reduce the levels of SERPING1 mRNA, ex vivo. In addition, we found that 30% of the SERPING1 genes network is upregulated in monocytes from HIV-1+ patients. Noteworthy, the expression levels of IFITM1-an antiviral molecule belonging to the genes network-correlate positively with SERPING1 expression. Interestingly, the monocytes treatment with IFN-gamma, IFN-beta and IFN-alpha significantly upregulates the SERPING1 mRNA expression levels. CONCLUSIONS: From the outcome of our investigation, it is possible to conclude that SERPING1 and its network serve as important components of the innate immune system to restrict HIV-1 infection.
OBJECTIVE: The HIV-1 virus activates the complement system, an essential element of the immune system. SERPING1 is a protease inhibitor that disables C1r/C1s in the C1 complex of the classical complement pathway. METHODS: In this paper, we performed an analysis of several microarrays deposited in GEO dataset to demonstrate that SERPING1 mRNA is modulated in CD14+ monocytes from HIV-1-infected individuals. In addition, data were validated on monocytes isolated from seronegative healthy volunteers, treated with IFNs. RESULTS: Our analysis shows that SERPING1 mRNA is overexpressed in monocytes from HIV-1+ patients and the expression levels correlate positively with viral load and negatively with the CD4+ T-cell count. Of note, anti-retroviral therapy is able to reduce the levels of SERPING1 mRNA, ex vivo. In addition, we found that 30% of the SERPING1 genes network is upregulated in monocytes from HIV-1+ patients. Noteworthy, the expression levels of IFITM1-an antiviral molecule belonging to the genes network-correlate positively with SERPING1 expression. Interestingly, the monocytes treatment with IFN-gamma, IFN-beta and IFN-alpha significantly upregulates the SERPING1 mRNA expression levels. CONCLUSIONS: From the outcome of our investigation, it is possible to conclude that SERPING1 and its network serve as important components of the innate immune system to restrict HIV-1 infection.
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