Targeted plasma proteomics identifies MICA and IL1R1 proteins associated with HIV-1 reservoir size
Marc J.T. Blaauw,
Jéssica Cristina dos Santos,
Nadira Vadaq,
Wim Trypsteen,
Wouter van der Heijden,
Albert Groenendijk,
Zhenhua Zhang,
Yang Li,
Quirijn de Mast,
Mihai G. Netea,
Leo A.B. Joosten,
Linos Vandekerckhove,
Andre van der Ven,
Vasiliki Matzaraki
Affiliations
Marc J.T. Blaauw
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands
Jéssica Cristina dos Santos
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands
Nadira Vadaq
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands; Center for Tropical and Infectious Diseases (CENTRID), Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia
Wim Trypsteen
HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
Wouter van der Heijden
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands
Albert Groenendijk
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands; Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, the Netherlands
Zhenhua Zhang
Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
Yang Li
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands; Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
Quirijn de Mast
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands
Mihai G. Netea
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands; Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
Leo A.B. Joosten
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
Linos Vandekerckhove
HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
Andre van der Ven
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands
Vasiliki Matzaraki
Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands; Corresponding author
Summary: HIV-1 reservoir shows high variability in size and activity among virally suppressed individuals. Differences in the size of the viral reservoir may relate to differences in plasma protein concentrations. We tested whether plasma protein expression levels are associated with levels of cell-associated (CA) HIV-1 DNA and RNA in 211 virally suppressed people living with HIV (PLHIV). Plasma concentrations of FOLR1, IL1R1, MICA, and FETUB showed a positive association with CA HIV-1 RNA and DNA. Moreover, SNPs in close proximity to IL1R1 and MICA genes were found to influence the levels of CA HIV-1 RNA and DNA. We found a difference in mRNA expression of the MICA gene in homozygotes carrying the rs9348866-A allele compared to the ones carrying the G allele (p < 0.005). Overall, our findings pinpoint plasma proteins that could serve as potential targets for therapeutic interventions to lower or even eradicate cells containing CA HIV-1 RNA and DNA in PLHIV.
