Volume 26, Issue 6 (11-2022)                   IBJ 2022, 26(6): 485-491 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Hamidi Y, Aliasgari E, Basimi P, Sajadipour M, Baesi K. Immune-Related Gene Profile in HIV-Infected Patients with Discordant Immune Response. IBJ 2022; 26 (6) :485-491
URL: http://ibj.pasteur.ac.ir/article-1-3750-en.html
Background: In spite of many reports on persistent low CD4 T cell counts and change in immune-related gene expression level in patients with HIV infection, there is still uncertainty about significant association between gene expression level and HIV infection in patients with and without discordant immune response (DIR). The aim of this study was to compare the expression level of CD4, CCL5, IFN-γ, STAT1, APOBEC3G, CD45, and ICAM-1 genes in HIV-1-positive patients with and without DIR.
Methods: In this study, 30 HIV-1-positive patients (15 patients with and 15 patients without DIR [control group]) were included. PBMCs of the patients were collected through density radient centrifugation with Ficoll-Hypaque. RNeasy Plus Mini kit was used to extract RNA. Relative expression levels of CD4, CCL5, IFN-γ, STAT1, APOBEC3G, CD45, and ICAM-1 genes were evaluated by real-time PCR.  The data were analyzed using one-way ANOVA.
Results: CD4 T cell counts were significantly lower in DIR patients than the control group (p < 0.01). While there was no significant difference in the relative expression levels of CD4, CCL5, IFN-γ, STAT1, CD45, and ICAM-1 between patients with DIR and control group, APOBEC3G expression level was significantly higher in the patients with DIR as compare to the control group (p < 0.01).
Conclusion: Our findings suggest a significantly higher APOBEC3G expression level in patients with DIR, suggesting the potential role of APOBEC3G in patients with immunological discordance besides its suppressing role in HIV-1 infection. Confirmation of this hypothesis requires further research.
Keywords: Genes, HIV-1, Immunity, Patients

1. Said M, Bartlett A. Immune dysfunction and antiretroviral therapy challenges in children and adolescents living with human immunodeficiency virus. Innate immunity in health and disease 2021; https://doi.org/10.5772/intechopen.91667 [DOI:10.5772/intechopen.91667.]
2. Hileman CO, Nicholas T. Funderburg. Inflammation, immune activation, and antiretroviral therapy in HIV. Current Hiv/aids reports 2017; 14(3): 93-100. [DOI:10.1007/s11904-017-0356-x]
3. Leal L, Fehér C, Richart V, Torres B, García F. Antiretroviral therapy interruption (ATI) in HIV-1 infected patients participating in therapeutic vaccine trials: surrogate markers of virological response. Vaccines 2020; 8(3): 442. [DOI:10.3390/vaccines8030442]
4. Sempa, Joseph B., Lesaffre E, Nieuwoudt M. Cumulative viral load as a predictor of CD4+ T-cell response to antiretroviral therapy using Bayesian statistical models. PloS one 2019; 14(11): e0224723. [DOI:10.1371/journal.pone.0224723]
5. Ford N, Chiller T. CD4 cell count: a critical tool in the HIV response. Clinical infectious diseases 2021; 74(8): 1360-1361. [DOI:10.1093/cid/ciab658]
6. Tibúrcio A S. Immunovirologic discordant response in patient beginning antiretroviral therapy. American journal of clinical and medical case reports 2021; 1(1): 1002.
7. Guillén Y, Noguera-Julian M, Rivera J, Casadellà M, Zevin AS, Rocafort M, Parera M, Rodríguez C, Arumí M, Carrillo J, Mothe B, Estany C, Coll J, Bravo I, Herrero C, Saz J, Sirera G, Torrella A, Navarro J, Crespo M, Negredo E, Brander C, Blanco J, Luz Calle M, Klatt NR, Clotet B, Paredes R. Low nadir CD4+ T-cell counts predict gut dysbiosis in HIV-1 infection. Mucosal immunology 2012; 12(1): 232-246. [DOI:10.1038/s41385-018-0083-7]
8. Kelly, Christine, Gaskell KM, Richardson M, Klein N, Garner P, MacPherson P. Discordant immune response with antiretroviral therapy in HIV-1: a systematic review of clinical outcomes. PloS one 2016; 1(6): e0156099. [DOI:10.1371/journal.pone.0156099]
9. Umar, Abdullahi, Oripelaye MM, Olanrewaju FO, Onayemi O, Olasode OA, Oninla OA. Determinants of discordant immune response in a cohort of human immunodeficiency virus-infected patients initiating antiretroviral therapy. Sahel medical journal 2020; 23(1): 22. [DOI:10.4103/smj.smj_1_19]
10. Shannon RR, Noon-Song EN, Yamamoto JK. The significance of interferon-γ in HIV-1 pathogenesis, therapy, and prophylaxis. Frontiers in immunology 2014; 4: 498. [DOI:10.3389/fimmu.2013.00498]
11. Chesarino NM, Emerman M. HIV-1 Vif gained breadth in APOBEC3G specificity after cross-species transmission of its precursors. Journal of virology 2022; 96(4): e0207121. [DOI:10.1128/jvi.02071-21]
12. Bishop KN, Verma M, Kim E-Y, Wolinsky SM, Malim MH. APOBEC3G inhibits elongation of HIV-1 reverse transcripts. PLoS pathogens 2008; 4(12): e1000231. [DOI:10.1371/journal.ppat.1000231]
13. Covino DA, Purificato C, Catapano L, Galluzzo CM, Gauzzi MC, Vella S, Lefebvre E, Seyedkazemi S, Andreotti M, Fantuzzi L. APOBEC3G/3A expression in human immunodeficiency virus type 1-infected individuals following initiation of antiretroviral therapy containing cenicriviroc or efavirenz. Frontiers in immunology 2018; 9: 1839. [DOI:10.3389/fimmu.2018.01839]
14. Pollpeter D, Parsons M, Sobala AE, Coxhead S, Lang RD, Bruns AM, Papaioannou S, McDonnell JM, Apolonia L, Chowdhury JA, Horvath CM, Malim MH. Deep sequencing of HIV-1 reverse transcripts reveals the multifaceted antiviral functions of APOBEC3G. Nature microbiology 2018; 3(2): 220-233. [DOI:10.1038/s41564-017-0063-9]
15. Reis EC, da Silva LT, da Silva WC, Rios A, Duarte AJ, Oshiro TM, Crovella S, Pontillo A. Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy. Humman vaccines immune theraputics 2018; 14(8): 1995-2002. [DOI:10.1080/21645515.2018.1463942]
16. Jin X, Brooks A, Chen H, Bennett R, Reichman R, Smith H. APOBEC3G/CEM15 (hA3G) mRNA levels associate inversely with human immunodeficiency virus viremia. Journal of virology 2005; 79(17): 11513-11516. [DOI:10.1128/JVI.79.17.11513-11516.2005]
17. Zhan Z, Zhang L, Shen Y. Identification of immune features of HIV-infected patients with antiretroviral therapy through bioinformatics analysis. Virology 2022; 566: 69-74. [DOI:10.1016/j.virol.2021.11.010]
18. Lee D, Yoon CH, Choi SY, Kim JE, Cho YC, Choi BS, Park J. Transcriptome analysis identifies altered biological processes and novel markers in human immunodeficiency virus-1 long-term non-progressors. Infection and chemotherapy 2021; 53(3): 489. [DOI:10.3947/ic.2021.0031]
19. Jabea Ekabe C, Asaba Clinton N, Kusi Agyei E, Kehbila J. Role of Apoptosis in HIV Pathogenesis. Advances in virology 2022; 2022: 8148119. [DOI:10.1155/2022/8148119]
20. Szodoray P, Kristian Andersen T , Heinzelbecker J, Imbery JF, Huszthy PC, Stanford SM, Bogen B, Landsverk OB, Bottini O, Tveita A, Munthe LA, Nakken B. Integration of T helper and BCR signals governs enhanced plasma cell differentiation of memory B cells by regulation of CD45 phosphatase activity. Cell reports 2021; 36(6): 109525. [DOI:10.1016/j.celrep.2021.109525]
21. Harris DP, Goodrich S, Gerth AJ, Peng SL, Lund FE. Regulation of IFN-γ production by B effector 1 cells: essential roles for T-bet and the IFN-γ receptor. The journal of immunology 5005; 174(11): 6781-6790. [DOI:10.4049/jimmunol.174.11.6781]
22. Howe MK, Dowdell K, Kuehn HS, Li Q, Hart GT, Garabedian D, Liepshutz K, Hsu EP, Su H, Niemela JE, Stoddard JL, Uzel G, Shereck E, Schulz L, Feldman T, Rosenzweig SD, Long EO, Dropulic L, Cohen JI. Patients with natural killer (NK) cell chronic active Epstein-Barr virus have immature NK cells and hyperactivation of PI3K/Akt/mTOR and STAT1 pathways. The Journal of infectious diseases 2020; 222(7): 1170-1179. [DOI:10.1093/infdis/jiaa232]
23. Mehlotra R K. New knowledge about CCR5, HIV infection, and disease progression: Is "Old" still valuable? AIDS research and human retroviruses 2020; 36(10): 795-799. [DOI:10.1089/aid.2020.0060]
24. Kozlovski S, Atrakchi O, Feigelson SW, Shulman Z, Alon R. Stable contacts of naïve CD4 T cells with migratory dendritic cells are ICAM-1-dependent but dispensable for proliferation in vivo. Cell adhesion and migration 2019; 13(1): 314-320. [DOI:10.1080/19336918.2019.1644857]
25. de Almeida Baptista MV, Teodoro da Silva L, Samer S, Miyuki Oshiro T, Luca Shytaj I, Giron LB, Mantovani Pena N, Cruz N, Gosuen GC, Abrão Ferreira PR, Cunha-Neto E, Galinskas J, Dias D, Araripe Sucupira MC, de Almeida-Neto C, Salomão R, José da Silva Duarte A, Mário Janini L, Hunter JR, Savarino A, Aparecida Juliano M, Sobhie Diaz R. Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial. AIDS research and therapy 2022; 19(1): 1-15. [DOI:10.1186/s12981-021-00426-z]
26. da Ressureição Sgnotto F, Souza Santos L, de Sousa TR, de Lima JF, da Silva Oliveira LM, Saeed Sanabani S, José da Silva Duarte A, Russo Victor J. IgG From HIV-1-Exposed Seronegative and HIV-1-Infected Subjects Differently Modulates IFN-γ Production by Thymic T and B Cells. JAIDS journal of acquired immune deficiency syndromes 2019; 82(5): e56-e60. [DOI:10.1097/QAI.0000000000002182]
27. Watanabe D, Uehira T, Yonemoto H, Bando H, Ogawa Y, Yajima K, Taniguchi T, Kasai D, Nishida Y, Shirasaka T. Sustained high levels of serum interferon-γ during HIV-1 infection: a specific trend different from other cytokines. Viral immunology 2010; 23(6): 619-625. [DOI:10.1089/vim.2010.0065]
28. Zhang Z, Perković M, Gu Q, Balakrishnan K, Sangwiman A, Häussinger D, Lindemann D, Münk C. HIV-2 Vif and foamy virus Bet antagonize APOBEC3B by different mechanisms. Virology 2021; 554: 17-27. [DOI:10.1016/j.virol.2020.11.013]
29. Marques RE, Guabiraba R, Castro Russo R, Martins Teixeira M. Targeting CCL5 in inflammation. Expert opinion on therapeutic targets 2013; 17(12): 1439-1460. [DOI:10.1517/14728222.2013.837886]
30. Donatella A, Borghese C, Casagrande N. The CCL5/CCR5 axis in cancer progression. Cancers 2020; 12(7): 1765. [DOI:10.3390/cancers12071765]
31. Kwon Y, Kaake RM, Echeverria L,Suarez M, Karimian Shamsabadi M, Stoneham C, Ramirez PW, Kress J, Singh R, Sali A, Krogan N, Guatelli A, Jia X. Structural basis of CD4 downregulation by HIV-1 Nef. Nature structural and molecular biology 2020; 27(9): 822-828. [DOI:10.1038/s41594-020-0463-z]
32. Cen S, Peng ZG, Li XY, Li ZR, Ma J, Wang JM, Fan B, You XF, Wang YP, Liu F, Shao RJ, Zhao LX, Yu L, Jiang JD. Small molecular compounds inhibit HIV-1 replication through specifically stabilizing APOBEC3G. Journal of biological chemistry 2010; 285(22): 16546-16552. [DOI:10.1074/jbc.M109.085308]

Add your comments about this article : Your username or Email:

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Iranian Biomedical Journal

Designed & Developed by : Yektaweb