title: Metabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte-derived macrophages.
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.
authors.affiliation: Center for Drug Discovery, Department of Pediatrics, Health Sciences Research Building, Emory University, 1760 Haygood Drive, Atlanta, GA 30322, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hollenbaugh
authors.affiliation: Center for Drug Discovery, Department of Pediatrics, Health Sciences Research Building, Emory University, 1760 Haygood Drive, Atlanta, GA 30322, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Montero
authors.affiliation: Center for Drug Discovery, Department of Pediatrics, Health Sciences Research Building, Emory University, 1760 Haygood Drive, Atlanta, GA 30322, USA.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14627, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Munger
authors.affiliation: Center for Drug Discovery, Department of Pediatrics, Health Sciences Research Building, Emory University, 1760 Haygood Drive, Atlanta, GA 30322, USA; Department of Pharmacy, Kyung-Hee University, Seoul, South Korea; Children's Healthcare of Atlanta, Emory University, Atlanta, GA 30322, USA. Electronic address: baek.kim@emory.edu.
authors.forename: Baek
authors.initials: B
authors.lastname: Kim
mesh_terms: D002478:Cells, Cultured; D002952:Citric Acid Cycle; D006019:Glycolysis; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D055442:Metabolome; D009000:Monocytes / Q000378:metabolism* / Q000821:virology
keywords: Glycolysis; HIV-1; HIV-2; LC–MS/MS; Macrophages; Metabolites; TCA