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Sharifi Z, Yadgari A, Paz Z. The level of expression of programmed death type 1 during the natural course of hepatitis B virus infection in asymptomatic carriers of hepatitis B. Sci J Iran Blood Transfus Organ 2024; 21 (4) :273-280
URL: http://bloodjournal.ir/article-1-1559-en.html
The level of expression of programmed death type 1 during the natural course of hepatitis B virus infection in asymptomatic carriers of hepatitis B
Z. Sharifi * , A. Yadgari , Z. Paz
Keywords: Key words: Hepatitis B Virus, Real-Time PCR, Asymptomatic Infections
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    References:
  1. Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med 2004 ; 350(11): 1118-29.
  2. Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet 2003; 20; 362(9401): 2089-94.
  3. Bertoletti A, Maini M, Williams R. Role of hepatitis B virus-specific cytotoxic T cells in liver damage and viral control. Antiviral Res 2003; 60(2): 61-6.
  4. Chisari FV,  Ferrari C. Hepatitis B Virus Immunopathogenesis.  Annu Rev Immunol 1995 13: 29-60.
  5. Maini MK, Boni C, Ogg GS, King AS, Reignat S, Lee CK, et al. Direct ex vivo analysis of hepatitis B virus-specific CD8(+) T cells associated with the control of infection. Gastroenterology 1999; 117(6): 1386-96.
  6. Yuen MF, Chen DS, Dusheiko GM, Janssen HLA, Lau DTY, Locarnini SA, et al. Hepatitis B virus infection. Nat Rev Dis Primers 2018; 4: 18035.
  7. Boni C, Fisicaro P, Valdatta C, Amadei B, Di Vincenzo P, Giuberti T, et al. Characterization of hepatitis B Virus (HBV)-Specific T-Cell Dysfunction in Chronic HBV Infection. J Virol 2007; 81(42): 15-25.
  8. Ai L, Chen J, Yan H, He Q, Luo P, Xu Z, et al. Research status and outlook of pd-1/pd-l1 inhibitors for cancer therapy. Drug Des Devel Ther 2020; 14: 3625-49.
  9. Chen Y, Pei Y, Luo J, Huang Z, Yu J, Meng X. Looking for the optimal PD-1/PD-L1 inhibitor in cancer treatment: A comparison in basic structure, function, and clinical practice. Front Immunol 2020; 11:1088.
  10. Bengsch B, Martin B, Thimme R. Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation. J   Hepatol 2014; 61: 1212-9.
  11. Singh V, Khurana A, Allawadhi P, Banothu AK, Bharani KK, Weiskirchen R. Emerging role of PD-1/PD-L1 inhibitors in chronic liver diseases. Front Pharmacol 2021; 12: 790963.
  12. Wieland S, Thimme R, Purcell RH, Chisari FV. Genomic analysis of the host response to hepatitis B virus infection. Proc Natl Acad Sci U S A 2004; 101(17): 6669-74.
  13. Wykes MN, Lewin SR. Immune checkpoint blockade in infectious diseases. Nat Rev Immunol 2018; 18(2): 91-104. 
  14. Cox MA, Nechanitzky R, Mak TW. Check point inhibitors as therapies for infectious diseases. Curr Opin Immunol 2017; 48: 61-7.
  15. Schönrich G, Raftery MJ. The PD-1/PD-L 1axis and virus infections: a delicate balance. Front Cell Infect Microbiol 2019; 9: 207.
  16. Ortega-Prieto AM, Dorner M. Immune Evasion Strategies during Chronic Hepatitis B and C Virus Infection. Vaccines (Basel) 2017; 5(3): 24.
  17. Ye P, Weng ZH, Zhang SL, Zhang JA, Zhao L, Dong JH, et al. Programmed death-1 expression is associated with the disease status in hepatitis B virus infection. World J Gastroenterol 2008; 14: 4551-7.  
  18. Liang XS, Zhou Y, Li CZ, Wan MB. Natural course of chronic hepatitis B is characterized by changing patterns  of   programmed death type-1 of CD8-positive  T cells. World J Gastroenterol 2010; 16(5): 618-24.
  19. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 2006; 443: 350-4.  
  20. Petrovas C, Casazza JP, Brenchley JM, Price DA, Gostick E, Adams WC, et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J Exp Med 2006; 203: 2281-92.  
  21. Zhang JY, Zhang Z, Wang X, Fu JL, Yao J, Jiao Y, et al. PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors. Blood 2007; 109: 4671-8.
  22. Golden-Mason L, Palmer B, Klarquist J, Mengshol JA, Castelblanco N, Rosen HR. Upregulation of PD-1 expression on circulating and intrahepatic hepatitis C virus-specific CD8+ T cells associated with reversible
    immune dysfunction. J Virol 2007; 81: 9249-58.  
  23. Urbani S, Amadei B, Tola D, Massari M, Schivazappa S, Missale G, et al. PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J Virol 2006; 80: 11398-403.  
  24. Boni C, Fisicaro P, Valdatta C, Amadei B, Di Vincenzo P, Giuberti T, et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol 2007; 81: 4215-25.
  25. Zhou JY, Zhou DF, Li JQ. PD-1 expression in HBcAg-specific CD8+ T cells of adolescents with chronic HBV infection. Zhonghua Gan Zang Bing Za Zhi 2013; 21(1): 27-32. [Article in Chinese]
  26. Cui D , Jiang D ,  Yan C ,  Liu X , Lv Y ,  Xie J, Chen Y. Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative. Front Microbiol 2022; 13: 887408.





 







Sci J Iran Blood Transfus Organ 2024; 21 (4): 273-280
Original Article
 








The level of expression of programmed death type 1
 during the natural course of hepatitis B virus infection
in asymptomatic carriers of hepatitis B

Sharifi Z.1, Yadgari A.1, Paz Z.1


1Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran


Abstract
Background and Objectives
During chronic hepatitis B virus infection, the dynamic balance between virus replication and the host immune response is crucial in developing liver disease. In this study, the level of expression of programmed death type 1 in asymptomatic donors infected with hepatitis B during the natural course of the infection was investigated.

Materials and Methods
In this case-control study, 120 blood donors were divided into two groups. The first control group included 60 healthy individuals who tested negative for HBsAg and anti-HBc. The second group, known as the case group, comprised 60 asymptomatic HBV-infected blood donors who tested positive for HBsAg and anti-HBc. All participants were entered from the Tehran Blood Center in 2018. To check gene expression after RNA extraction and cDNA synthesis, a Real-Time PCR test was performed for the PD-1 gene and β-actin reference gene, then using REST software, gene expression changes compared to the healthy group were checked.

Results
All the samples of asymptomatic HBV-infected blood donors were 100% positive for total anti-HBc, anti-HBe, and negative for HBe Ag. The gene expression levels were analyzed using REST software, utilizing Cycle Threshold  values obtained from Real-Time PCR tests for the PD-1 gene and a reference gene. The analysis revealed 1.5 times increase in PD-1 gene expression in asymptomatic HBV-infected donors compared to healthy donors. However, this increase was not found to be statistically significant.

Conclusions 
PD-1 gene expression does not change during the normal course of chronic HBV infection in asymptomatic HBV-infected donors and is similar to healthy individuals.

Key words: Hepatitis B Virus, Real-Time PCR, Asymptomatic Infections





Received:  8 Oct 2024
Accepted: 3 Nov 2024



Correspondence: Sharifi Z., PhD of Virology. Professor of Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine.           
P.O.Box: 14665-1157, Tehran, Iran. Tel: (+9821) 82052152; Fax: (+9821) 88601555
E-mail: sharifiz@yahoo.com
 
Type of Study: Research | Subject: Virology
Published: 2024/12/30
References
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20. Petrovas C, Casazza JP, Brenchley JM, Price DA, Gostick E, Adams WC, et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J Exp Med 2006; 203: 2281-92. [DOI:10.1084/jem.20061496] [PMID] []
21. Zhang JY, Zhang Z, Wang X, Fu JL, Yao J, Jiao Y, et al. PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors. Blood 2007; 109: 4671-8. [DOI:10.1182/blood-2006-09-044826] [PMID]
22. Golden-Mason L, Palmer B, Klarquist J, Mengshol JA, Castelblanco N, Rosen HR. Upregulation of PD-1 expression on circulating and intrahepatic hepatitis C virus-specific CD8+ T cells associated with reversible immune dysfunction. J Virol 2007; 81: 9249-58. [DOI:10.1128/JVI.00409-07] [PMID] []
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24. Boni C, Fisicaro P, Valdatta C, Amadei B, Di Vincenzo P, Giuberti T, et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol 2007; 81: 4215-25. [DOI:10.1128/JVI.02844-06] [PMID] []
25. Zhou JY, Zhou DF, Li JQ. PD-1 expression in HBcAg-specific CD8+ T cells of adolescents with chronic HBV infection. Zhonghua Gan Zang Bing Za Zhi 2013; 21(1): 27-32. [Article in Chinese]
26. Cui D , Jiang D , Yan C , Liu X , Lv Y , Xie J, Chen Y. Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative. Front Microbiol 2022; 13: 887408. [DOI:10.3389/fmicb.2022.887408] [PMID] []
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