Blaauw Marc J T, Cristina Dos Santos Jéssica, Vadaq Nadira, Trypsteen Wim, van der Heijden Wouter, Groenendijk Albert, Zhang Zhenhua, Li Yang, de Mast Quirijn, Netea Mihai G, Joosten Leo A B, Vandekerckhove Linos, van der Ven Andre, Matzaraki Vasiliki
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.
iScience. 2023 Mar 22;26(4):106486. doi: 10.1016/j.isci.2023.106486. eCollection 2023 Apr 21.
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 and genes were found to influence the levels of CA HIV-1 RNA and DNA. We found a difference in mRNA expression of the 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.
在病毒抑制的个体中,HIV-1储存库在大小和活性方面表现出高度变异性。病毒储存库大小的差异可能与血浆蛋白浓度的差异有关。我们在211名病毒抑制的HIV感染者(PLHIV)中测试了血浆蛋白表达水平是否与细胞相关(CA)HIV-1 DNA和RNA水平相关。FOLR1、IL1R1、MICA和FETUB的血浆浓度与CA HIV-1 RNA和DNA呈正相关。此外,发现靠近 和 基因的单核苷酸多态性(SNP)会影响CA HIV-1 RNA和DNA的水平。我们发现,携带rs9348866 - A等位基因的纯合子与携带G等位基因的纯合子相比, 基因的mRNA表达存在差异(p < 0.005)。总体而言,我们的研究结果确定了血浆蛋白,这些蛋白可作为治疗干预的潜在靶点,以降低甚至根除PLHIV中含有CA HIV-1 RNA和DNA的细胞。