HIV-2 mediated effects on target and bystander cells induce plasma proteome remodeling

HIV-2 mediated effects on target and bystander cells induce plasma proteome remodeling

Emil Johansson ^1 2, Jamirah Nazziwa ^1 2, Eva Freyhult ³, Mun-Gwan Hong ⁴, Jacob Lindman ⁵, Malin Neptin ^1 2, Sara Karlson ^2 6, Melinda Rezeli ⁷, Antonio J Biague ⁸, Patrik Medstrand ^1 2, Fredrik Månsson ¹, Hans Norrgren ⁵, Joakim Esbjörnsson ^1 2 9, Marianne Jansson ^2 6; SWEGUB CORE group

Affiliations

• ¹Department of Translational Medicine, Lund University, Lund, Sweden.
• ²Lund University Virus Centre, Lund, Sweden.
• ³Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
• ⁴National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
• ⁵Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
• ⁶Department of Laboratory Medicine, Lund University, Lund, Sweden.
• ⁷BioMS - Swedish National Infrastructure for Biological Mass Spectrometry, Lund University, Lund, Sweden.
• ⁸National Public Health Laboratory, Bissau, Guinea-Bissau.

• ⁹Nuffield Department of Medicine, University of Oxford, Oxford, UK.

   

• PMID: 38500818
• PMCID: PMC10945182
• DOI: 10.1016/j.isci.2024.109344

Abstract

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.

Keywords: Disease; Human specimen; Proteomics; Virology.