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

doi:10.1016/j.isci.2023.106486

Targeted plasma proteomics identifies MICA and IL1R1 proteins associated with HIV-1 reservoir size

iScience. 2023 Mar 22;26(4):106486. doi: 10.1016/j.isci.2023.106486. eCollection 2023 Apr 21.

Authors

Marc J T Blaauw¹, Jéssica Cristina Dos Santos¹, Nadira Vadaq^{1

2}, Wim Trypsteen³, Wouter van der Heijden¹, Albert Groenendijk^{1

4}, Zhenhua Zhang⁵, Yang Li^{1

5

6}, Quirijn de Mast¹, Mihai G Netea^{1

7}, Leo A B Joosten^{1

8}, Linos Vandekerckhove³, Andre van der Ven¹, Vasiliki Matzaraki¹

Affiliations

¹ Radboud University Medical Center, Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands.
² Center for Tropical and Infectious Diseases (CENTRID), Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia.
³ HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
⁴ Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, the Netherlands.
⁵ 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.
⁶ 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.
⁷ Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
⁸ Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Abstract

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.

Keywords: Health sciences; Proteomics; Virology.