Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection
Abstract
:1. Introduction
2. Experimental Section
2.1. Samples
2.2. Small RNA Extraction
2.3. Next-Generation Sequencing
2.4. Analysis of miRNA
2.5. miRNA Alignment
2.6. Differential Expression Analysis
2.7. Target Genes Identification and Functional Analysis
3. Results
3.1. Patient Characteristics
3.2. Next-Generation Sequencing Quality Assessment
3.3. miRNA Mapping
3.4. Global Comparison
3.5. Differences in miRNA Expression Associated with Viral Replication
3.6. Differences in miRNA Expression Associated with Disease Progression
3.7. Differences of miRNA Expression Associated with EC-LTNP Phenotype
3.8. Potentially Altered Pathways Regulated by DE miRNA Associated with Disease Progression
3.8.1. DE miRNA Predictably Targets Various Genes Involved in the KEGG HIV-1 Infection Pathway
3.8.2. Enrichment Analysis of Likely Altered Pathways Based on HIV-1 Human Interaction Database
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Group | Patient ID | Sex | Origin | CD4+ T Cell Count (Cell/mm3) | Via of Infection | HCV Co-Infection |
---|---|---|---|---|---|---|
EC-LTNP | EC-LTNP-1 | M | European | 635 | IDU | Yes |
EC-LTNP-2 | M | European | 555 | IDU | Yes | |
EC-LTNP-3 | F | European | 596 | IDU | Yes | |
EC-LTNP-4 | F | European | 1081 | SEX | No | |
EC-LTNP-5 | F | European | 603 | SEX | Yes | |
EC-LTNP-6 | M | European | 640 | IDU | Yes | |
EC-LTNP-7 | M | European | 514 | IDU | Yes | |
EC-LTNP-8 | M | European | 708 | IDU | Yes | |
vLTNP | vLTNP-1 | M | European | 625 | SEX | No |
vLTNP-2 | M | European | 590 | IDU | Yes | |
vLTNP-3 | M | European | 1049 | IDU | Yes | |
vLTNP-4 | M | European | 593 | IDU | Yes | |
vLTNP-5 | F | European | 492 | IDU | Yes | |
vLTNP-6 | M | European | NA | SEX | No | |
vLTNP-7 | M | European | 889 | IDU | No | |
vLTNP-8 | M | European | 929 | IDU | Yes | |
pre-TP | pre-TP-1 | M | European | 290 | IDU | Yes |
pre-TP-2 | M | European | 332 | SEX | No | |
pre-TP-3 | M | European | 397 | SEX | No | |
pre-TP-4 | F | European | 270 | SEX | No | |
pre-TP-5 | M | European | 624 | SEX | No | |
pre-TP-6 | M | European | 157 | SEX | No | |
pre-TP-7 | M | European | 47 | SEX | No | |
post-TP | post-TP-1 | M | European | 720 | IDU | Yes |
post-TP-2 | M | European | 525 | SEX | No | |
post-TP-3 | M | European | 550 | SEX | No | |
post-TP-4 | F | European | 650 | SEX | No | |
post-TP-5 | M | European | 439 | SEX | No | |
post-TP-6 | M | European | 415 | SEX | No | |
post-TP-7 | M | European | 578 | SEX | No |
Group | Gene | miRNA | Expression Change | 3′ UTR Predicted Site | Canonical Site Types 1 | References 2 |
---|---|---|---|---|---|---|
pre-TP vs. post-TP | SOCS2 | miR-424-5p | ↓ | 2253–2259 | 7mer-1A | [38,39] |
HIF1A | miR-18b-5p | ↓ | 409–415 | 7mer-m8 | [40,41] | |
AKT1 | miR-374b-5p | ↓ | 2434–2440 | 7mer-1A | [42,43] | |
WNT16 | miR-374b-5p | ↓ | 1262–1269 | 8mer | ||
LTNP vs. TP | RAB14 | miR-144-5p | ↓ | 361–367 | 7mer-m8 | [44,45] |
miR-144-3p | ↓ | 1052–1058 | 7mer-1A | |||
miR-451a | ↓ | 3207–3213 | 7mer-m8 | |||
DICER1 | miR-18a-5p | ↓ | 1201–1208 | 7mer-m8 | [46,47] | |
↓ | 4300–4307 | 8mer | ||||
ING5 | miR-331-3p | ↓ | 4147–4154 | 8mer | [48,49,50] | |
MTORC1 | miR-99a-5p | ↑ | 295–301 | 7mer-m8 | [51,52] | |
DNMT3 | miR-450a-5p | ↓ | 649–655 | 7mer-1A | [53,54,55] | |
EC-LTNP vs. vLTNP | TRAF6 | miR-146a-5p | ↓ | 40–47 | 8mer | [56,57,58] |
IRAK1 | 473–480 | 8mer | ||||
PTEN | miR-1063 | ↓ | 272–278 | 7mer-m8 | [59,60] | |
IL21R | miR-30a-5p | ↑ | 125–132 | 8mer | [61,62] |
miRNA | log2(FC) | p-Value | q-Value |
---|---|---|---|
miR-3607-5p | −1.6073 | 0.00001 | 0.0064 |
miR-486-3p | −1.0910 | 0.00002 | 0.0071 |
miR-144-3p | −1.2943 | 0.0003 | 0.0892 |
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Ayala-Suárez, R.; Díez-Fuertes, F.; Calonge, E.; De La Torre Tarazona, H.E.; Gracia-Ruíz de Alda, M.; Capa, L.; Alcamí, J. Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection. J. Clin. Med. 2020, 9, 2452. https://doi.org/10.3390/jcm9082452
Ayala-Suárez R, Díez-Fuertes F, Calonge E, De La Torre Tarazona HE, Gracia-Ruíz de Alda M, Capa L, Alcamí J. Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection. Journal of Clinical Medicine. 2020; 9(8):2452. https://doi.org/10.3390/jcm9082452
Chicago/Turabian StyleAyala-Suárez, Rubén, Francisco Díez-Fuertes, Esther Calonge, Humberto Erick De La Torre Tarazona, María Gracia-Ruíz de Alda, Laura Capa, and José Alcamí. 2020. "Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection" Journal of Clinical Medicine 9, no. 8: 2452. https://doi.org/10.3390/jcm9082452