MiRNA expression profiling in HIV pathogenesis, disease progression and response to treatment: a systematic review
Abstract
Aim: A systematic review was conducted to identify the association of miRNA expression with HIV pathogenesis, progression and treatment. Methods: A search of articles was conducted in MEDLINE®, Cochrane Central Register of Controlled Trials and Global Health. Results: 35 articles were included. Due to the heterogeneity of HIV phenotypes, a harmonization based on key progression parameters was proposed. The hsa-miR-29 family, hsa-miR-146b-5p and hsa-miR-150-5p, are the most frequently differentially expressed in HIV. Direct comparison of studies was not possible due to heterogeneity in biological samples and miRNA analysis techniques. Conclusion: This is the first attempt to systematically identify miRNA's different expression in well-defined patient phenotypes and could represent a helpful way to increase general knowledge in this field.
Lay abstract
miRNAs play important role in the regulation of gene expression and are involved in various physiological processes. Dysregulation of their function can lead to human diseases including cancer, cardiovascular and metabolic diseases, liver conditions and immune dysfunction. The aim of this work is to systematically analyze the current scientific literature to identify miRNAs linked to the mechanism, development and treatment of HIV. A total of 35 articles were included and the miRNAs that were found with significantly different levels in compared groups of subjects (e.g., subjects with HIV vs healthy persons, persons able to limit the disease progression without therapy vs those whose immune system is already compromised by HIV) were highlighted. The most frequently reported miRNAs were: the hsa-miR-29 family, hsa-miR-146b-5p and hsa-miR-150-5p. To our knowledge, this is the first attempt to systematically identify the miRNAs associated with HIV and could be a useful contribution to general knowledge in this field.
Papers of special note have been highlighted as: • of interest
References
- 1. . Basics of the virology of HIV-1 and its replication. J. Clin. Virol. 34(4), 233–244 (2005).
- 2. Impact of comorbidity and ageing on health-related quality of life in HIV-positive and HIV-negative individuals. AIDS 31(10), 1471–1481 (2017).
- 3. WHO. Number of people (all ages) living with HIV (2019). https://apps.who.int/gho/data/node.main.620?lang=en
- 4. . Highly active antiretroviral therapy (HAART). In: StatPearls [Internet]. StatPearls Publishing, FL, USA (2021).
- 5. . Quality of life of people living with HIV and AIDS and antiretroviral therapy. HIV/AIDS Res. Palliat. Care 4, 117 (2012).
- 6. International AIDS Society global scientific strategy: towards an HIV cure 2016. Nat. Med. 22(8), 839–850 (2016).
- 7. . Rates of emergence of HIV drug resistance in resource-limited settings: a systematic review. Antivir. Ther. 18(1), 115–123 (2012).
- 8. Achieving a cure for HIV infection: do we have reasons to be optimistic? J. Antimicrob. Chemother. 67(5), 1063–1074 (2012).
- 9. . MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol. Med. 20(8), 460–469 (2014).
- 10. . MicroRNAs in autoimmune diseases. Biomed Res. Int. 2014, 1–8 (2014).
- 11. . The involvement of microRNAs in neurodegenerative diseases. Front. Cell Neurosci. 7, 265 (2013).
- 12. . Circulating microRNAs as biomarkers for inflammatory diseases. MicroRNA 2(1), 64–72 (2013).
- 13. The expression of microRNAs and exposure to environmental contaminants related to human health: a review. Int. J. Environ. Health Res. 12, 1–23 (2020).
- 14. The influence of lifestyle factors on miRNA expression and signal pathways: a review. Epigenomics 13(2), 145–164 (2021).
- 15. . MicroRNAs and their potential involvement in HIV infection. Trends Pharmacol. Sci. 32(11), 675–681 (2011).
- 16. . The impact of microRNA expression on cellular proliferation. Hum. Genet. 133(7), 931–938 (2014).
- 17. . MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 27(45), 5959–5974 (2008).
- 18. . MicroRNAs in development and disease. Physiol. Rev. 91(3), 827–887 (2011).
- 19. . MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget 6(11), 8474–8490 (2015).
- 20. . microRNAs and the immune response. Trends Immunol. 29(7), 343–351 (2008).
- 21. . Roles of microRNAs in the life cycles of mammalian viruses. Curr. Topics Microbiol. Immunol. 371, 201–227 (2013).
- 22. . Robust global microRNA expression profiling using next-generation sequencing technologies. Lab. Investig. 94(3), 350–358 (2014).
- 23. MicroRNAs and exosomes: key players in HIV pathogenesis. HIV Med. 21(4), 246–278 (2020). • Reports miRNAs as important players in HIV pathogenesis with potential diagnostic applications as biomarkers in HIV infection.
- 24. . Deploying an interactive machine learning system in an evidence-based practice center: abstrackr. Presented at: ACM Int. Health Informat. Symposium (IHI). FL, USA, 28 – 30 January 2012.
- 25. Hyland Software. Alfresco – ECM and BPM Software | Alfresco (2021). www.alfresco.com/
- 26. A systematic review of definitions of extreme phenotypes of HIV control and progression. AIDS 28(2), 149–162 (2014). • Gives evidence of the heterogeneity in HIV phenotypes that may represent important differences in biological phenotypes and clinical progression profiles of individuals and suggests the need for harmonized definitions.
- 27. Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US Department of Defense HIV natural history study. J. Infect. Dis. 200(11), 1714–1723 (2009).
- 28. . miRBase: from microRNA sequences to function. Nucleic Acids Res. 47(D1), D155–D162 (2019).
- 29. . miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42(D1), D68–D73 (2014).
- 30. . miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 39 (Database), D152–D157 (2011).
- 31. . miRBase: tools for microRNA genomics. Nucleic Acids Res. 36 (Database), D154–D158 (2007).
- 32. . miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 34 (90001), D140–D144 (2006).
- 33. . The microRNA Registry. Nucleic Acids Res. 32(90001), 109D–111 (2004).
- 34. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339, b2700 (2009).
- 35. . miRWalk database for miRNA-target interactions. Methods Mol. Biol. 1182, 289–305 (2014).
- 36. . InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics 16(1), 169 (2015).
- 37. . Biological network exploration with Cytoscape 3. Curr. Protoc. Bioinforma. 47, 8.13.1–24 (2014).
- 38. MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survival. FASEB J. 24(6), 1799–1812 (2010).
- 39. MicroRNA-155 is a biomarker of T-cell activation and immune dysfunction in HIV-1-infected patients. HIV Med. 18(5), 354–362 (2017).
- 40. miR-29a associates with viro-immunological markers of HIV infection in treatment experienced patients. J. Med. Virol. 88(12), 2132–2137 (2016). • Reports an association between miR-29a expression levels and the virological and immunological markers of HIV-1 infection in antiretroviral treatment-experienced patients.
- 41. A parallel genome-wide mRNA and microRNA profiling of the frontal cortex of HIV patients with and without HIV-associated dementia shows the role of axon guidance and downstream pathways in HIV-mediated neurodegeneration. BMC Genomics 13, 677 (2012).
- 42. Stable changes in CD4+ T lymphocyte miRNA expression after exposure to HIV-1. Blood 119(26), 6259–6267 (2012).
- 43. Anti-HIV microRNA expression in a novel Indian cohort. Sci. Rep. 6, 28279 (2016).
- 44. Differential microRNA expression profile between stimulated PBMCs from HIV-1 infected elite controllers and viremic progressors. PLoS ONE 9(9), e106360 (2014).
- 45. MicroRNA profile in CD8+ T-lymphocytes from HIV-infected individuals: relationship with antiviral immune response and disease progression. PLoS ONE 11(5), e0155245 (2016).
- 46. Unique circulating microRNA profiles in HIV infection. J. Acquir. Immune Defic. Syndr. 79(5), 644–650 (2018).
- 47. The microRNA-9/B-lymphocyte-induced maturation protein-1/IL-2 axis is differentially regulated in progressive HIV infection. Eur. J. Immunol. 43(2), 510–520 (2013).
- 48. Differential regulation of the Let-7 family of microRNAs in CD4+ T cells alters IL-10 expression. J. Immunol. 188(12), 6238–6246 (2012).
- 49. . Relationships of PBMC microRNA expression, plasma viral load, and CD4+ T-cell count in HIV-1-infected elite suppressors and viremic patients. Retrovirology 9, 5 (2012).
- 50. Elevated expression of miR-19b enhances CD8(+) T cell function by targeting PTEN in HIV infected long term non-progressors with sustained viral suppression. Front. Immunol. 9, 3140 (2019).
- 51. The assessment of selected MiRNAs profile in HIV, HBV, HCV, HIV/HCV, HIV/HBV co-infection and elite controllers for determination of biomarker. Microb. Pathog. 147, 104355 (2020).
- 52. MicroRNA-29 family expression and its relation to antiviral immune response and viro-immunological markers in HIV-1-infected patients. BMC Infect Dis. 15, 51 (2015).
- 53. . MicroRNA-150 is a potential biomarker of HIV/AIDS disease progression and therapy. PLoS ONE 9(5), e95920 (2014). • Reports for the first time that levels of miR-150 and miR-146b-5p are predictive of HIV/AIDS disease progression and therapy.
- 54. . The microRNA miR-29a is associated with human immunodeficiency virus latency. Retrovirology 11, 108 (2014).
- 55. Plasma extracellular microRNAs are related to AIDS/cerebral toxoplasmosis co-infection. Parasite Immunol. 42(4), e12696 (2020). • Reports that gender could be an important factor in HIV-associated miRNAs.
- 56. . Overexpression of microRNAs from the miR-17-92 paralog clusters in AIDS-related non-Hodgkin's lymphomas. PLoS ONE 6(6), e20781 (2011).
- 57. MicroRNA-210, microRNA-331, and microRNA-7 are differentially regulated in treated HIV-1-infected individuals and are associated with markers of systemic inflammation. J. Acquir. Immune Defic. Syndr. 74(4), e104–e113 (2017).
- 58. . Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1. Mol. Med. Rep. 16(2), 1584–1589 (2017).
- 59. Antiretroviral therapy fails to restore levels of HIV-1 restriction miRNAs in PBMCs of HIV-1-infected MSM. Med. 94(46), e2116 (2015).
- 60. Exosomal microRNAs associate with neuropsychological performance in individuals with HIV infection on antiretroviral therapy. J. Acquir. Immune Defic. Syndr. 82(5), 514–522 (2019).
- 61. MicroRNA profiling in plasma of HIV-1 infected patients: potential markers of infection and immune status. J. Public Heal. Emerg. 1(7), (2017).
- 62. Changes in subcutaneous adipose tissue microRNA expression in HIV-infected patients. J. Antimicrob. Chemother. 69(11), 3067–3075 (2014).
- 63. Extracellular vesicles from T cells overexpress miR-146b-5p in HIV-1 infection and repress endothelial activation. Sci. Rep. 9(1), 10299 (2019).
- 64. . Development and validation of plasma miRNA biomarker signature panel for the detection of early HIV-1 infection. EBioMedicine 43, 307–316 (2019).
- 65. mircoRNA-3162-3p is a potential biomarker to identify new infections in HIV-1-infected patients. Gene 662, 21–27 (2018).
- 66. HIV disease, metabolic dysfunction and atherosclerosis: a three year prospective study. PLoS ONE 14(4), e0215620 (2019).
- 67. MicroRNAs profiling in HIV, HCV, and HIV/HCV co-infected patients. Curr. HIV Res. 19(1), 27–34 (2021).
- 68. Cerebrospinal fluid miRNA profile in HIV-encephalitis. J. Cell. Physiol. 228(5), 1070–1075 (2013).
- 69. B-cell activation induced microRNA-21 is elevated in circulating B cells preceding the diagnosis of AIDS-related non-Hodgkin lymphomas. AIDS 26(9), 1177–1180 (2012).
- 70. Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL. J. Acquir. Immune Defic. Syndr. 66(2), 229–237 (2014).
- 71. . MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease. Cell Death Dis. 1, e77 (2010).
- 72. Short Communication: HIV-1 infection suppresses circulating viral restriction microRNAs. AIDS Res. Hum. Retroviruses 32(4), 386–389 (2016).
- 73. . Imbalance in the game of T cells: what can the CD4/CD8 T-cell ratio tell us about HIV and health? PLoS Pathog. 13(11), e1006624 (2017).
- 74. Identification of a specific miRNA profile in HIV-exposed seronegative individuals. J. Acquir. Immune Defic. Syndr. 73(1), 11–19 (2016).
- 75. . miRNAs and HIV: unforeseen determinants of host-pathogen interaction. Immunol. Rev. 254(1), 265–280 (2013).
- 76. . MicroRNA detection: current technology and research strategies. Annu. Rev. Anal. Chem. (Palo Alto). 8, 217–237 (2015).
- 77. Technology in microRNA profiling: circulating microRNAs as noninvasive cancer biomarkers in breast cancer. J. Lab. Autom. 20(5), 574–588 (2015).
- 78. . Expression profiling of microRNA using real-time quantitative PCR, how to use it and what is available. Methods 50(4), 244–249 (2010).
- 79. . Updates on the current technologies for microRNA profiling. MicroRNA (Shariqah, UAE) 9, 17–24 (2019).
- 80. . Research progress in molecular biology related quantitative methods of microRNA. Am. J. Transl. Res. 12(7), 3198–3211 (2020). • Reports on the recent advances in miRNA expression analysis.
- 81. New trends in the development of electrochemical biosensors for the quantification of microRNAs. J. Pharm. Biomed. Anal. 189, 113478 (2020).
- 82. . MicroRNAs and HIV latency: a complex and promising relationship. AIDS Rev. 14(3), 188–94
- 83. . Differential activation and functional specialization of miR-146 and miR-155 in innate immune sensing. Nucleic Acids Res. 41(1), 542–553 (2013).
- 84. . Regulation of cyclin T1 and HIV-1 replication by MicroRNAs in resting CD4+ T lymphocytes. J. Virol. 86(6), 3244–3252 (2012).
- 85. Cellular microRNA expression correlates with susceptibility of monocytes/macrophages to HIV-1 infection. Blood 113(3), 671–674 (2009).
- 86. Comprehensive characterization of molecular differences in cancer between male and female patients. Cancer Cell 29(5), 711–722 (2016).
- 87. . Sexual dimorphism of miRNA expression: a new perspective in understanding the sex bias of autoimmune diseases. Ther. Clin. Risk Manag. 10, 151–163 (2014).
- 88. . Counteracting Akt activation by HIV protease inhibitors in monocytes/macrophages. Viruses 10(4), 190 (2018).
- 89. . Protein kinase B (PKB/Akt), a key mediator of the PI3K signaling pathway. Curr. Top. Microbiol. Immunol. 346, 31–56 (2010).
- 90. . Rho family GTPases and their regulators in lymphocytes. Nat. Rev. Immunol. 9(9), 630–644 (2009).
- 91. . HIV-1 hijacking of host ATPases and GTPases that control protein trafficking. Front. Cell Dev. Biol. 9, 622610 (2021).