Metabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte-derived macrophages

• Type of Material: Article
• Authors: Joseph Hollenbaugh, Emory University; Catherine Montero, Emory University; Raymond F Schinazi, Emory University; Joshua Munger, University of Rochester Medical Center; Baek Kim, Emory University
• Language: English
• Date: 2016-04-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2016.01.023
• Title of Journal or Parent Work: Virology
• ISSN: 0042-6822
• Volume: 491
• Start Page: 106
• End Page: 114
• Grant/Funding Information: This study was supported by NIH, USA AI049781 (B.K.), GM104198 (B. K.), AI081773 (J.M.), and MH100999 (R.F.S.).
• Keywords: Virology; Metabolites; LC-MS/MS; Life Sciences & Biomedicine; DISEASE; MYELOID CELLS; Science & Technology; PROTEIN; KYNURENINE PATHWAY; HIV-2; TYPE-1; HUMAN-IMMUNODEFICIENCY-VIRUS; CD4+T CELLS; TCA; HIV-1; Macrophages; DENDRITIC CELLS; VPX; Glycolysis; RESTRICTION FACTOR SAMHD1
• Research Categories: Chemistry, Biochemistry; Health Sciences, General; Health Sciences, Public Health

Abstract

We evaluated cellular metabolism profiles of HIV-1 and HIV-2 infected primary human monocyte-derived macrophages (MDMs). First, HIV-2 GL-AN displays faster production kinetics and greater amounts of virus as compared to HIV-1s: YU-2, 89.6 and JR-CSF. Second, quantitative LC-MS/MS metabolomics analysis demonstrates very similar metabolic profiles in glycolysis and TCA cycle metabolic intermediates between HIV-1 and HIV-2 infected macrophages, with a few notable exceptions. The most striking metabolic change in MDMs infected with HIV-2 relative to HIV-1-infected MDMs was the increased levels of quinolinate, a metabolite in the tryptophan catabolism pathway that has been linked to HIV/AIDS pathogenesis. Third, both HIV-1 and HIV-2 infected MDMs showed elevated levels of ribose-5-phosphate, a key metabolic component in nucleotide biosynthesis. Finally, HIV-2 infected MDMs display increased dNTP concentrations as predicted by Vpx-mediated SAMHD1 degradation. Collectively, these data show differential metabolic changes during HIV-1 and HIV-2 infection of macrophages.