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

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

Marc J T Blaauw  1 , Jéssica Cristina Dos Santos  1 , Nadira Vadaq  1   2 , Wim Trypsteen  3 , Wouter van der Heijden  1 , Albert Groenendijk  1   4 , Zhenhua Zhang  5 , Yang Li  1   5   6 , Quirijn de Mast  1 , Mihai G Netea  1   7 , Leo A B Joosten  1   8 , Linos Vandekerckhove  3 , Andre van der Ven  1 , Vasiliki Matzaraki  1
Affiliations

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

Marc J T Blaauw et al. iScience. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Spearman’s ρ correlation among HIV-1 reservoir traits (CA HIV-1 RNA and DNA) and clinical characteristics The top left triangle shows the ρ values, positive correlations are colored in red and negative correlations in blue. The bottom right triangle shows the FDR values of each correlation. Abbreviations: cART = combined antiretroviral therapy.
Figure 2
Figure 2
Association of protein plasma concentrations with HIV-1 reservoir traits (A and B) Volcano plot of proteins associated with (A) cell-associated HIV-1 DNA and (B) cell-associated HIV-1 RNA. A linear model with age and sex as covariates was used to quantify the association between plasma protein levels and HIV-1 reservoir traits. Horizontal dashed line represents an unadjusted p value < 0.05. Proteins showing a p value < 0.05 are depicted in red. The higher the effect size, the higher the levels of proteins.
Figure 3
Figure 3
Boxplot of relative expression of the MICA gene measured in whole blood samples in subjects carrying rs9348866-A (n = 22) versus rs9348866-T (n = 12) Relative mRNA expression is log transformed. Data are presented as median +/− IQR. Groups are compared by using the two-sample Wilcoxon test because of non-normal distribution.
Figure 4
Figure 4
Boxplot of plasma concentrations of MICA protein (A and B) Boxplot of plasma concentrations of MICA protein in (A) PLHIV (n = 61) versus individuals without HIV (n = 44) and (B) individuals with high CA HIV RNA and DNA (n = 24) versus individuals with low CA HIV RNA and DNA (n = 21). MICA concentrations are presented in pg/mL. Data are presented as median +/− IQR. Groups are compared by using the two-sample Wilcoxon test because of non-normal distribution.
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References

    1. Palella F.J., Jr., Delaney K.M., Moorman A.C., Loveless M.O., Fuhrer J., Satten G.A., Aschman D.J., Holmberg S.D. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N. Engl. J. Med. 1998;338:853–860. doi: 10.1056/NEJM199803263381301. - DOI - PubMed
    1. Davey R.T., Jr., Bhat N., Yoder C., Chun T.W., Metcalf J.A., Dewar R., Natarajan V., Lempicki R.A., Adelsberger J.W., Miller K.D., et al. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc. Natl. Acad. Sci. USA. 1999;96:15109–15114. doi: 10.1073/pnas.96.26.15109. - DOI - PMC - PubMed
    1. Chun T.W., Justement J.S., Murray D., Hallahan C.W., Maenza J., Collier A.C., Sheth P.M., Kaul R., Ostrowski M., Moir S., et al. Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication. AIDS. 2010;24:2803–2808. doi: 10.1097/QAD.0b013e328340a239. - DOI - PMC - PubMed
    1. Chomont N., El-Far M., Ancuta P., Trautmann L., Procopio F.A., Yassine-Diab B., Boucher G., Boulassel M.R., Ghattas G., Brenchley J.M., et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat. Med. 2009;15:893–900. doi: 10.1038/nm.1972. - DOI - PMC - PubMed
    1. Bruner K.M., Murray A.J., Pollack R.A., Soliman M.G., Laskey S.B., Capoferri A.A., Lai J., Strain M.C., Lada S.M., Hoh R., et al. Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat. Med. 2016;22:1043–1049. doi: 10.1038/nm.4156. - DOI - PMC - PubMed

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