Login Register Cart 0
Generic placeholder image

Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Assessment of Key Elements in the Innate Immunity System Among Patients with HIV, HCV, and Coinfections of HIV/HCV

Author(s): Maryam Moradi, Alireza Tabibzadeh, Davod Javanmard, Saied Ghorbani, Farah Bokharaei-Salim, Hosein Keivani, Mohammad Khazeni and Seyed Hamid Reza Monavari*

Volume 18, Issue 3, 2020

Page: [194 - 200] Pages: 7

DOI: 10.2174/1570162X18999200325162533

Price: $65

Abstract

Background: Coinfection of Hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has a higher risk of mortality than HCV or HIV monoinfection. HCV and HIV infections are specified by systemic inflammation, but the inflammation process in HCV/HIV coinfection is much complicated and is not well characterized.

Objective: The aim of this study was to analyze the expression of TLR-3, TLR-7, IL-10, IFN-1 (IFN-α, IFN-β), and TNF-α in HIV, HCV and HIV/HCV co-infected patients.

Methods: Forty-five patients including HIV group (n=15), HCV group (n=15), HIV/HCV coinfection group (n=15) and healthy control group (n=15) participated. Peripheral blood mononuclear cells (PBMCs) were obtained. PBMC-RNA, HCV and HIV RNA were extracted from all subjects and cDNA was synthesized. The viral load analyzed by reverse transcription-quantitative PCR (RT-qPCR), and the expression levels of IFN-α, IFN-β, TLR-3, TLR-7, TNF, and IL-10 mRNA were quantified in PBMCs.

Results: The levels of IFN-I, IL-10, and TNF-α were overexpressed in all patients’ groups (p<0.05), TLR-7 was upregulated in all groups, but this upregulation was not statistically significant (p>0.05). TLR-3 showed a decrease in all patient groups (p<0.05). The statistical analysis demonstrated that TLR-3 has a negative correlation with HIV load, whereas other genes positively correlated with HIV load. In addition, TLR-3, TNF-α, and IFN-I were negatively correlated with HCV load, whereas TLR-7 and IL-10 s were positively correlated with HCV load.

Conclusion: Our results showed a significant relationship between the expression level of innate immunity genes and inflammation in HCV, HIV, and HIV/HCV coinfected patients.

Keywords: HIV, HCV, Coinfection, TLR-3, TLR-7, IL-10, IFN-I, TNF-α.

« Previous Next »
Graphical Abstract

[1]
Dayan S, Özekinci T, Bekçibaşi M, Deveci Ö. HBsAg, anti-HCV and anti-HIV seroprevalence among blood donors in Southeastern Anatolia, Turkey, 2011-2015. Infez Med 2019; 27(3): 316-21.
[PMID: 31545776]
[2]
Rosenthal E, Poirée M, Pradier C, et al. Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study). AIDS 2003; 17(12): 1803-9.
[http://dx.doi.org/10.1097/00002030-200308150-00009] [PMID: 12891066]
[3]
Rockstroh JK, Spengler U. HIV and hepatitis C virus co-infection. Lancet Infect Dis 2004; 4(7): 437-44.
[http://dx.doi.org/10.1016/S1473-3099(04)01059-X] [PMID: 15219554]
[4]
Bastani MN, Bokharaei-Salim F, Keyvani H, et al. Prevalence of occult hepatitis C virus infection in Iranian patients with beta thalassemia major. Arch Virol 2016; 161(7): 1899-906.
[http://dx.doi.org/10.1007/s00705-016-2862-3] [PMID: 27132015]
[5]
El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012; 142(6): 1264-73.
[http://dx.doi.org/10.1053/j.gastro.2011.12.061] [PMID: 22537432]
[6]
Keyvani H, Fazlalipour M, Monavari SH, Mollaie HR. Hepatitis C virus--proteins, diagnosis, treatment and new approaches for vaccine development. Asian Pac J Cancer Prev 2012; 13(12): 5931-49.
[PMID: 23464383]
[7]
Hernandez MD, Sherman KE. HIV/hepatitis C coinfection natural history and disease progression. Curr Opin HIV AIDS 2011; 6(6): 478-82.
[http://dx.doi.org/10.1097/COH.0b013e32834bd365] [PMID: 22001892]
[8]
Sulkowski MS. Viral hepatitis and HIV coinfection. J Hepatol 2008; 48(2): 353-67.
[http://dx.doi.org/10.1016/j.jhep.2007.11.009] [PMID: 18155314]
[9]
Bokharaei-Salim F, Keyvani H, Monavari SH, Alavian SM, Fakhim S, Nasseri S. Distribution of hepatitis C virus genotypes among azerbaijani patients in capital city of iran-tehran. Hepat Mon 2013; 13(9) e13699
[http://dx.doi.org/10.5812/hepatmon.13699] [PMID: 24282427]
[10]
Ziaee M, Zarban A, Malekinejad P, Akhbary H. Evaluation of HGV Viremia Prevalence and Its Co-Infection with HBV, HCV, HIV and HTLV-1 in Hemophilic Patients of Southern Khorassan, Iran. Hepat Mon 2007; 7(1): 11-4.
[11]
Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010; 11(5): 373-84.
[http://dx.doi.org/10.1038/ni.1863] [PMID: 20404851]
[12]
Lund JM, Alexopoulou L, Sato A, et al. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 2004; 101(15): 5598-603.
[http://dx.doi.org/10.1073/pnas.0400937101] [PMID: 15034168]
[13]
Heil F, Hemmi H, Hochrein H, et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004; 303(5663): 1526-9.
[http://dx.doi.org/10.1126/science.1093620] [PMID: 14976262]
[14]
Sadeghi F, Bokharaei-Salim F, Salehi-Vaziri M, et al. Associations between human TRIM22 gene expression and the response to combination therapy with Peg-IFNα-2a and ribavirin in Iranian patients with chronic hepatitis C. J Med Virol 2014; 86(9): 1499-506.
[http://dx.doi.org/10.1002/jmv.23985] [PMID: 24889558]
[15]
Xu Y, Zhong J. Innate immunity against hepatitis C virus. Curr Opin Immunol 2016; 42: 98-104.
[http://dx.doi.org/10.1016/j.coi.2016.06.009] [PMID: 27366996]
[16]
Silvin A, Manel N. Innate immune sensing of HIV infection. Curr Opin Immunol 2015; 32: 54-60.
[http://dx.doi.org/10.1016/j.coi.2014.12.003] [PMID: 25617674]
[17]
Lei J, Hilgenfeld R. RNA-virus proteases counteracting host innate immunity. FEBS Lett 2017; 591(20): 3190-210.
[http://dx.doi.org/10.1002/1873-3468.12827] [PMID: 28850669]
[18]
Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001; 413(6857): 732-8.
[http://dx.doi.org/10.1038/35099560] [PMID: 11607032]
[19]
Oshiumi H, Matsumoto M, Funami K, Akazawa T, Seya T. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol 2003; 4(2): 161-7.
[http://dx.doi.org/10.1038/ni886] [PMID: 12539043]
[20]
Yamamoto M, Sato S, Hemmi H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 2003; 301(5633): 640-3.
[http://dx.doi.org/10.1126/science.1087262] [PMID: 12855817]
[21]
Yamamoto M, Sato S, Mori K, et al. Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 2002; 169(12): 6668-72.
[http://dx.doi.org/10.4049/jimmunol.169.12.6668] [PMID: 12471095]
[22]
Fateh A, Aghasadeghi MR, Keyvani H, et al. High resolution melting curve assay for detecting rs12979860 IL28B polymorphisms involved in response of Iranian patients to chronic hepatitis C treatment. Asian Pac J Cancer Prev 2015; 16(5): 1873-80.
[http://dx.doi.org/10.7314/APJCP.2015.16.5.1873] [PMID: 25773839]
[23]
O’Neill LA, Golenbock D, Bowie AG. The history of Toll-like receptors - redefining innate immunity. Nat Rev Immunol 2013; 13(6): 453-60.
[http://dx.doi.org/10.1038/nri3446] [PMID: 23681101]
[24]
Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol 2012; 32(1): 23-63.
[http://dx.doi.org/10.1615/CritRevImmunol.v32.i1.30] [PMID: 22428854]
[25]
Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683-765.
[http://dx.doi.org/10.1146/annurev.immunol.19.1.683] [PMID: 11244051]
[26]
Liberto MC, Zicca E, Pavia G, et al. Virological Mechanisms in the Coinfection between HIV and HCV. Mediators Inflamm 2015; 2015 320532
[http://dx.doi.org/10.1155/2015/320532] [PMID: 26494946]
[27]
Vahabpour R, Bokharaei-Salim F, Kalantari S, et al. HIV-1 genetic diversity and transmitted drug resistance frequency among Iranian treatment-naive, sexually infected individuals. Arch Virol 2017; 162(6): 1477-85.
[http://dx.doi.org/10.1007/s00705-017-3228-1] [PMID: 28181034]
[28]
Lin W, Weinberg EM, Chung RT. Pathogenesis of accelerated fibrosis in HIV/HCV co-infection. J Infect Dis 2013; 207(Suppl. 1): S13-8.
[http://dx.doi.org/10.1093/infdis/jis926] [PMID: 23390300]
[29]
Sohrab SS, Suhail M, Ali A, Qadri I, Harakeh S, Azhar EI. Consequence of HIV and HCV co-infection on host immune response, persistence and current treatment options. Virusdisease 2018; 29(1): 19-26.
[http://dx.doi.org/10.1007/s13337-018-0424-x] [PMID: 29607354]
[30]
Bokharaei-Salim F, Keyvani H, Salehi-Vaziri M, et al. Mutations in the NS5A gene of hepatitis C virus subtype 1b and response to peg-IFNα-2a/RBV combination therapy in Azerbaijani patients. Arch Virol 2014; 159(11): 2893-9.
[http://dx.doi.org/10.1007/s00705-014-2133-0] [PMID: 25139545]
[31]
Curry MP. HIV and hepatitis C virus: special concerns for patients with cirrhosis. J Infect Dis 2013; 207(Suppl. 1): S40-4.
[http://dx.doi.org/10.1093/infdis/jis763] [PMID: 23390304]
[32]
Barrett L, Gallant M, Howley C, et al. Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals. BMC Immunol 2008; 9: 28.
[http://dx.doi.org/10.1186/1471-2172-9-28] [PMID: 18554409]
[33]
Brockman MA, Kwon DS, Tighe DP, et al. IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells. Blood 2009; 114(2): 346-56.
[http://dx.doi.org/10.1182/blood-2008-12-191296] [PMID: 19365081]
[34]
Nelson DR, Lauwers GY, Lau JY, Davis GL. Interleukin 10 treatment reduces fibrosis in patients with chronic hepatitis C: a pilot trial of interferon nonresponders. Gastroenterology 2000; 118(4): 655-60.
[http://dx.doi.org/10.1016/S0016-5085(00)70134-X] [PMID: 10734016]
[35]
Nelson DR, Tu Z, Soldevila-Pico C, et al. Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect. Hepatology 2003; 38(4): 859-68.
[http://dx.doi.org/10.1002/hep.1840380412] [PMID: 14512873]
[36]
Garcia-Broncano P, Medrano LM, Berenguer J, et al. Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status. Cells 2018; 7(11): 196.
[http://dx.doi.org/10.3390/cells7110196] [PMID: 30400258]
[37]
Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010; 10(3): 170-81.
[http://dx.doi.org/10.1038/nri2711] [PMID: 20154735]
[38]
Bam RA, Hansen D, Irrinki A, et al. TLR7 Agonist GS-9620 Is a Potent Inhibitor of Acute HIV-1 Infection in Human Peripheral Blood Mononuclear Cells. Antimicrob Agents Chemother 2016; 61(1): e01369-16.
[http://dx.doi.org/10.1128/AAC.01369-16] [PMID: 27799218]
[39]
Baenziger S, Heikenwalder M, Johansen P, et al. Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology. Blood 2009; 113(2): 377-88.
[http://dx.doi.org/10.1182/blood-2008-04-151712] [PMID: 18824599]
[40]
Levy DE, Marié IJ, Durbin JE. Induction and function of type I and III interferon in response to viral infection. Curr Opin Virol 2011; 1(6): 476-86.
[http://dx.doi.org/10.1016/j.coviro.2011.11.001] [PMID: 22323926]
[41]
Jiménez-Sousa MA, Rallón N, Berenguer J, et al. TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients. J Clin Virol 2015; 65: 62-7.
[http://dx.doi.org/10.1016/j.jcv.2015.02.004] [PMID: 25766991]
[42]
Berzsenyi MD, Roberts SK, Preiss S, et al. Hepatic TLR2 & TLR4 expression correlates with hepatic inflammation and TNF-α in HCV & HCV/HIV infection. J Viral Hepat 2011; 18(12): 852-60.
[http://dx.doi.org/10.1111/j.1365-2893.2010.01390.x] [PMID: 21050341]
[43]
Waters JP, Pober JS, Bradley JR. Tumour necrosis factor in infectious disease. J Pathol 2013; 230(2): 132-47.
[http://dx.doi.org/10.1002/path.4187] [PMID: 23460469]
[44]
Dolganiuc A, Oak S, Kodys K, et al. Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation. Gastroenterology 2004; 127(5): 1513-24.
[http://dx.doi.org/10.1053/j.gastro.2004.08.067] [PMID: 15521019]
[45]
Helbig KJ, Ruszkiewicz A, Lanford RE, et al. Differential expression of the CXCR3 ligands in chronic hepatitis C virus (HCV) infection and their modulation by HCV in vitro. J Virol 2009; 83(2): 836-46.
[http://dx.doi.org/10.1128/JVI.01388-08] [PMID: 18987152]
[46]
Tilton JC, Johnson AJ, Luskin MR, et al. Diminished production of monocyte proinflammatory cytokines during human immunodeficiency virus viremia is mediated by type I interferons. J Virol 2006; 80(23): 11486-97.
[http://dx.doi.org/10.1128/JVI.00324-06] [PMID: 17005663]
[47]
Villacres MC, Kono N, Mack WJ, et al. Interleukin 10 responses are associated with sustained CD4 T-cell counts in treated HIV infection. J Infect Dis 2012; 206(5): 780-9.
[http://dx.doi.org/10.1093/infdis/jis380] [PMID: 22693231]
[48]
Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, Roederer M. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 2005; 434(7037): 1093-7.
[http://dx.doi.org/10.1038/nature03501] [PMID: 15793563]
[49]
Shmagel K, Saidakova E. Immune Disorders in HIV-Infected Patients Coinfected with Hepatitis C Virus. Advances in HIV and AIDS Control: IntechOpen 2018.https://www.intechopen.com/books/advances-in-hiv-and-aids-control/immune-disorders-in-hiv-infected-patients-coinfected-with-hepatitis-c-virus
[50]
Komatsuda A, Wakui H, Iwamoto K, et al. Up-regulated expression of Toll-like receptors mRNAs in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Clin Exp Immunol 2008; 152(3): 482-7.
[http://dx.doi.org/10.1111/j.1365-2249.2008.03646.x] [PMID: 18373699]
[51]
McAllister CS, Toth AM, Zhang P, Devaux P, Cattaneo R, Samuel CE. Mechanisms of protein kinase PKR-mediated amplification of beta interferon induction by C protein-deficient measles virus. J Virol 2010; 84(1): 380-6.
[http://dx.doi.org/10.1128/JVI.02630-08] [PMID: 19846517]
[52]
Mendez C, Kramer AA, Salhab KF, et al. Tolerance to shock: An exploration of mechanism. Ann Surg 1999; 229(6): 843-9.
[http://dx.doi.org/10.1097/00000658-199906000-00011] [PMID: 10363898]

Rights & Permissions Print Cite
Article Metrics
7
© 2024 Bentham Science Publishers | Privacy Policy