HIV-2 mediated effects on target and bystander cells induce plasma proteome remodeling
Emil Johansson,
Jamirah Nazziwa,
Eva Freyhult,
Mun-Gwan Hong,
Jacob Lindman,
Malin Neptin,
Sara Karlson,
Melinda Rezeli,
Antonio J. Biague,
Patrik Medstrand,
Fredrik Månsson,
Hans Norrgren,
Joakim Esbjörnsson,
Marianne Jansson
Affiliations
Emil Johansson
Department of Translational Medicine, Lund University, Lund, Sweden; Lund University Virus Centre, Lund, Sweden
Jamirah Nazziwa
Department of Translational Medicine, Lund University, Lund, Sweden; Lund University Virus Centre, Lund, Sweden
Eva Freyhult
Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Mun-Gwan Hong
National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
Jacob Lindman
Department of Clinical Sciences Lund, Lund University, Lund, Sweden
Malin Neptin
Department of Translational Medicine, Lund University, Lund, Sweden; Lund University Virus Centre, Lund, Sweden
Sara Karlson
Lund University Virus Centre, Lund, Sweden; Department of Laboratory Medicine, Lund University, Lund, Sweden
Melinda Rezeli
BioMS – Swedish National Infrastructure for Biological Mass Spectrometry, Lund University, Lund, Sweden
Antonio J. Biague
National Public Health Laboratory, Bissau, Guinea-Bissau
Patrik Medstrand
Department of Translational Medicine, Lund University, Lund, Sweden; Lund University Virus Centre, Lund, Sweden
Fredrik Månsson
Department of Translational Medicine, Lund University, Lund, Sweden
Hans Norrgren
Department of Clinical Sciences Lund, Lund University, Lund, Sweden
Joakim Esbjörnsson
Department of Translational Medicine, Lund University, Lund, Sweden; Lund University Virus Centre, Lund, Sweden; Nuffield Department of Medicine, University of Oxford, Oxford, UK; Corresponding author
Marianne Jansson
Lund University Virus Centre, Lund, Sweden; Department of Laboratory Medicine, Lund University, Lund, Sweden; Corresponding author
Summary: Despite low or undetectable plasma viral load, people living with HIV-2 (PLWH2) typically progress toward AIDS. The driving forces behind HIV-2 disease progression and the role of viremia are still not known, but low-level replication in tissues is believed to play a role. To investigate the impact of viremic and aviremic HIV-2 infection on target and bystander cell pathology, we used data-independent acquisition mass spectrometry to determine plasma signatures of tissue and cell type engagement. Proteins derived from target and bystander cells in multiple tissues, such as the gastrointestinal tract and brain, were detected at elevated levels in plasma of PLWH2, compared with HIV negative controls. Moreover, viremic HIV-2 infection appeared to induce enhanced release of proteins from a broader range of tissues compared to aviremic HIV-2 infection. This study expands the knowledge on the link between plasma proteome remodeling and the pathological cell engagement in tissues during HIV-2 infection.
