Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1

dc.creatorAzevedo, Suwellen S. D.
dc.creatorRibeiro-Alves, Marcelo
dc.creatorCôrtes, Fernanda H.
dc.creatorDelatorre, Edson
dc.creatorSpangenberg, Lucia
dc.creatorNaya, Hugo
dc.creatorSeito, Leonardo N.
dc.creatorHoagland, Brenda
dc.creatorGrinsztejn, Beatriz
dc.creatorVeloso, Valdiléa G.
dc.creatorMorgado, Mariza G.
dc.creatorSouza, Thiago Moreno L.
dc.creatorBello, Gonzalo
dc.date2020-08-31T23:58:05Z
dc.date2020-08-31T23:58:05Z
dc.date2020
dc.date.accessioned2023-09-26T20:17:57Z
dc.date.available2023-09-26T20:17:57Z
dc.identifierAzevedo, Suwellen S. D. et al. Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1. Retrovirology, v. 17, n. 1, p. 1-14, 2020.
dc.identifier1742-4690
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/43100
dc.identifier10.1186/s12977-020-00522-4
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8853645
dc.descriptionBackground: Some multifunctional cellular proteins, as the monocyte chemotactic protein-induced protein 1 (ZC3H12A/MCPIP1) and the cyclin-dependent kinase inhibitor CDKN1A/p21, are able to modulate the cellular susceptibility to the human immunodeficiency virus type 1 (HIV-1). Several studies showed that CDKN1A/p21 is expressed at high levels ex vivo in cells from individuals who naturally control HIV-1 replication (HIC) and a recent study supports a coordinate regulation of ZC3H12A/MCPIP1 and CDKN1A/p21 transcripts in a model of renal carcinoma cells. Here, we explored the potential associations between mRNA expression of ZC3H12A/MCPIP1 and CDKN1A/p21 in HIC sustaining undetectable (elite controllers-EC) or low (viremic controllers-VC) viral loads. Results: We found a selective upregulation of ZC3H12A/MCPIP1 and CDKN1A/p21 mRNA levels in PBMC from HIC compared with both ART-suppressed and HIV-negative control groups (P≤ 0.02) and higher MCPIP1 and p21 proteins levels in HIC than in HIV-1 negative subjects. There was a moderate positive correlation (r ≥ 0.57; P ≤ 0.014) between expressions of both transcripts in HIC and in HIC combined with control groups. We found positive correlations between the mRNA level of CDKN1A/p21 with activated CD4+ T cells levels in HIC (r ≥ 0.53; P ≤ 0.017) and between the mRNA levels of both CDKN1A/p21 (r = 0.74; P = 0.005) and ZC3H12A/MCPIP1 (r = 0.58; P = 0.040) with plasmatic levels of sCD14 in EC. Reanalysis of published transcriptomic data confirmed the positive association between ZC3H12A/MCPIP1 and CDKN1A/p21 mRNA levels in CD4+ T cells and monocytes from disparate cohorts of HIC and other HIV-positive control groups. Conclusions: These data show for the first time the simultaneous upregulation of ZC3H12A/MCPIP1 and CDKN1A/p21 transcripts in the setting of natural suppression of HIV-1 replication in vivo and the positive correlation of the expression of these cellular factors in disparate cohorts of HIV-positive individuals. The existence of a common regulatory pathway connecting ZC3H12A/MCPIP1 and CDKN1A/p21 could have a synergistic effect on HIV-1 replication control and pharmacological manipulation of these multifunctional host factors may open novel therapeutic perspectives to prevent HIV-1 replication and disease progression.
dc.formatapplication/pdf
dc.languageeng
dc.publisherBMC
dc.rightsopen access
dc.subjectHIV-1 controllers
dc.subjectImmune activation
dc.subjectMCPIP1
dc.subjectRestriction factors
dc.subjectp21
dc.titleIncreased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1
dc.typeArticle


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