| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | de Azevedo, Suwellen S. D. Ribeiro-Alves, Marcelo Côrtes, Fernanda H. Delatorre, Edson Spangenberg, Lucia Naya, Hugo Seito, Leonardo N. Hoagland, Brenda Grinsztejn, Beatriz Veloso, Valdilea G. Morgado, Mariza G. Souza, Thiago Moreno L. Bello, Gonzalo |
| Abstract | Background 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. |
| Related Links | https://retrovirology.biomedcentral.com/counter/pdf/10.1186/s12977-020-00522-4.pdf |
| Ending Page | 14 |
| Page Count | 14 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17424690 |
| DOI | 10.1186/s12977-020-00522-4 |
| Journal | Retrovirology |
| Issue Number | 1 |
| Volume Number | 17 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2020-07-02 |
| Access Restriction | Open |
| Subject Keyword | Virology Infectious Diseases Cancer Research Vaccine Antibodies Protein Structure HIV-1 controllers Restriction factors MCPIP1 p21 Immune activation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Virology |
| Journal Impact Factor | 2.7/2023 |
| 5-Year Journal Impact Factor | 3.1/2023 |
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