title: In Vivoandin VitroProteome Analysis of Human Immunodeficiency Virus (HIV)-1-infected, Human CD4+T Cells.
abstract: Host-directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Because HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+T cells upon HIV-1 infection, bothin vitroandin vivoA SWATH-MS approach was used to measure the proteome of human primary CD4+T cells infected with HIV-1in vitroas well as CD4+T cells from HIV-1-infected patients with paired samples on and off antiretroviral treatment. In thein vitroexperiment, the proteome of CD4+T cells was quantified over a time course following HIV-1 infection. 1,725 host cell proteins and 4 HIV-1 proteins were quantified, with 145 proteins changing significantly during the time course. Changes in the proteome peaked 24 h after infection, concomitantly with significant HIV-1 protein production. In thein vivobranch of the study, CD4+T cells from viremic patients and those with no detectable viral load after treatment were sorted, and the proteomes were quantified. We consistently detected 895 proteins, 172 of which were considered to be significantly different between the viremic patients and patients undergoing successful treatment. The proteome of thein vitro-infected CD4+T cells was modulated on multiple functional levels, including TLR-4 signaling and the type 1 interferon signaling pathway. Perturbations in the type 1 interferon signaling pathway were recapitulated in CD4+T cells from patients. The study shows that proteome maps generated by SWATH-MS indicate a range of functionally significant changes in the proteome of HIV-infected human CD4+T cells. Exploring these perturbations in more detail may help identify new targets for immune based interventions.
authors.affiliation: From the ‡Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich 8091.|§Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich CH-8093.
authors.forename: Johannes
authors.initials: J
authors.lastname: Nemeth
authors.affiliation: From the ‡Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich 8091.|‖Institute of Medical Virology, University of Zurich, Zurich 8057, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vongrad
authors.affiliation: From the ‡Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich 8091.|‖Institute of Medical Virology, University of Zurich, Zurich 8057, Switzerland.
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Metzner
authors.affiliation: From the ‡Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich 8091.|‖Institute of Medical Virology, University of Zurich, Zurich 8057, Switzerland.
authors.forename: Victoria P
authors.initials: VP
authors.lastname: Strouvelle
authors.affiliation: From the ‡Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich 8091.
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.affiliation: §Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich CH-8093.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pedrioli
authors.affiliation: §Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich CH-8093.|**Faculty of Science, University of Zurich, Zurich 8057; and.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.affiliation: From the ‡Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich 8091; collins@imsb.biol.ethz.ch huldrych.guenthard@usz.ch.|‖Institute of Medical Virology, University of Zurich, Zurich 8057, Switzerland.
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.affiliation: §Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich CH-8093; collins@imsb.biol.ethz.ch huldrych.guenthard@usz.ch.
authors.forename: Ben C
authors.initials: BC
authors.lastname: Collins
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D020543:Proteome