Integrative proteo-transcriptomic and immunophenotyping signatures of HIV-1 elite control phenotype: A cross-talk between glycolysis and HIF signaling
Sara Svensson Akusjärvi,
Anoop T. Ambikan,
Shuba Krishnan,
Soham Gupta,
Maike Sperk,
Ákos Végvári,
Flora Mikaeloff,
Katie Healy,
Jan Vesterbacka,
Piotr Nowak,
Anders Sönnerborg,
Ujjwal Neogi
Affiliations
Sara Svensson Akusjärvi
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, 141 52 Stockholm, Sweden; Corresponding author
Anoop T. Ambikan
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, 141 52 Stockholm, Sweden
Shuba Krishnan
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, 141 52 Stockholm, Sweden
Soham Gupta
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, 141 52 Stockholm, Sweden
Maike Sperk
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, 141 52 Stockholm, Sweden
Ákos Végvári
Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Campus Solna, 171 65 Stockholm, Sweden
Flora Mikaeloff
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, 141 52 Stockholm, Sweden
Katie Healy
Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, 141 52 Stockholm, Sweden
Jan Vesterbacka
Department of Medicine Huddinge, Division of Infectious Disease, Karolinska Institutet, I73, Karolinska University Hospital, 141 86 Stockholm, Sweden
Piotr Nowak
Department of Medicine Huddinge, Division of Infectious Disease, Karolinska Institutet, I73, Karolinska University Hospital, 141 86 Stockholm, Sweden
Anders Sönnerborg
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, 141 52 Stockholm, Sweden; Department of Medicine Huddinge, Division of Infectious Disease, Karolinska Institutet, I73, Karolinska University Hospital, 141 86 Stockholm, Sweden
Ujjwal Neogi
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, 141 52 Stockholm, Sweden; Manipal Institute of Virology (MIV), Manipal Academy of Higher Education, Manipal, Karnataka, India; Corresponding author
Summary: Natural control of HIV-1 is a characteristic of <1% of HIV-1-infected individuals, so called elite controllers (EC). In this study, we sought to identify signaling pathways associated with the EC phenotype using integrative proteo-transcriptomic analysis and immunophenotyping. We found HIF signaling and glycolysis as specific traits of the EC phenotype together with dysregulation of HIF target gene transcription. A higher proportion of HIF-1α and HIF-1β in the nuclei of CD4+ and CD8+ T cells in the male EC were observed, indicating a potential increased activation of the HIF signaling pathway. Furthermore, intracellular glucose levels were elevated in EC even as the surface expression of the metabolite transporters Glut1 and MCT-1 were decreased on lymphocytes indicative of unique metabolic uptake and flux profile. Combined, our data show that glycolytic modulation and altered HIF signaling is a unique feature of the male EC phenotype that may contribute to natural control of HIV-1.