Association of TAP1 and TAP2 polymorphisms with the outcome of persistent HBV infection in a northeast Han Chinese population

Qiu, Bing; Huang, Bo; Wang, Xi; Liang, Jinlong; Feng, Jinfa; Chang, Yingjuan; Li, Dongfu

doi:10.3109/00365521.2012.725090

Cited by 8 publications

(7 citation statements)

References 26 publications

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“…These complexes are trafficked via the trans-Golgi to the plasma membrane, where they are recognized by the T lymphocyte cell receptor (TCR) (13,18). The importance of TAPs and tapasin for expression of HBV CTL epitopes as well as IPR for IFN␥-activated MHC class I-restricted antigen presentation on hepatocytes has been previously reported (11,39), and TAP polymorphism plays a significant role in infection outcomes (59). Particularly, HBV core peptide 18 -27 (FLPSDEFPSV) has been characterized as a CTL epitope (4,5,43,57) with therapeutic potential (8,63).…”

Section: Introductionmentioning

confidence: 99%

Acetaldehyde suppresses the display of HBV-MHC class I complexes on HBV-expressing hepatocytes

Ganesan

Krutik

Makarov

et al. 2019

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hepatitis B virus (HBV) infection and alcoholism are major public health problems worldwide, contributing to the development of end-stage liver disease. Alcohol intake affects HBV infection pathogenesis and treatment outcomes. HBV-specific cytotoxic T lymphocytes (CTLs) play an important role in HBV clearance. Many previous studies have focused on alcohol-induced impairments of the immune response. However, it is not clear whether alcohol alters the presentation of HBV peptide-major histocompatibility complex (MHC) class I complexes on infected hepatocytes resulting in escape of its recognition by CTLs. Hence, the focus of this study was to investigate the mechanisms by which ethanol metabolism affects the presentation of CTL epitope on HBV-infected hepatocytes. As demonstrated here, although continuous cell exposure to acetaldehyde-generating system (AGS) increased HBV load in HepG2.2.15 cells, it decreased the expression of HBV core peptide 18–27-human leukocyte antigen-A2complex (CTL epitope) on the cell surface. Moreover, we observed AGS-induced suppression of chymotrypsin- and trypsin-like proteasome activities necessary for peptide processing by proteasome as well as a decline in IFNγ-stimulated immunoproteasome (IPR) function and expression of PA28 activator and immunoproteasome subunits LMP7 and LMP2. Furthermore, IFNγ-induced activation of peptide-loading complex (PLC) components, such as transporter associated with antigen processing (TAP1) and tapasin, were suppressed by AGS. The attenuation of IPR and PLC activation was attributed to AGS-triggered impairment of IFNγ signaling in HepG2.2.15 cells. Collectively, all these downstream events reduced the display of HBV peptide-MHC class I complexes on the hepatocyte surface, which may suppress CTL activation and the recognition of CTL epitopes on HBV-expressing hepatocytes by immune cells, thereby leading to persistence of liver inflammation. NEW & NOTEWORTHY Our study shows that in HBV-expressing HepG2.2.15 cells, acetaldehyde alters HBV peptide processing by suppressing chymotrypsin- and trypsin-like proteasome activities and decreases IFNγ-stimulated immunoproteasome function and expression of PA28 activator and immunoproteasome subunits. It also suppresses IFNγ-induced activation of peptide-loading complex (PLC) components due to impairment of IFNγ signaling via the JAK-STAT1 pathway. These acetaldehyde-induced dysfunctions reduced the display of HBV peptide-MHC class I complexes on the hepatocyte surface, thereby leading to persistence of HBV infection.

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Section: Introductionmentioning

confidence: 99%

Acetaldehyde suppresses the display of HBV-MHC class I complexes on HBV-expressing hepatocytes

Ganesan

Krutik

Makarov

et al. 2019

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

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“…Our group has recently found an association between a TAP1 gene polymorphism with recurrent respiratory papillomatosis 18 . Other studies on polymorphisms in the TAP gene have reported an increased susceptibility to hepatitis B virus (HBV), HIV and human papillomavirus (HPV) infections 19 , 20 .…”

Section: Discussionmentioning

confidence: 99%

Association of TAP1 1177A>G and 2090A>G gene polymorphisms with latent tuberculosis infections in sheltered populations, in the metropolitan area of Guadalajara, Mexico: a pilot study

Cazarez‐Navarro

Palomares‐Marin

Rodríguez-Preciado

et al. 2021

Rev. Inst. Med. trop. S. Paulo

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“…Both TAP 1 and TAP 2 polymorphisms may result in TAP1/2 protein deficiency (reported for rs 1057141, rs 1135216 and rs 241447), which leads to bare lymphocyte syndrome ( 35 ). They were also found to be associated with chronic infections and impaired antigen clearance, which could potentially lead to chronic exposure to potentially harmful substances, and enhance the risk of persistent lung damage ( 36 ). Exposure to inhalation of antigens, as well as their role in IPF pathogenesis, has been widely discussed as an important trigger of lung injury, followed by impaired healing ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of genotype on the disease course in idiopathic pulmonary fibrosis despite antifibrotic treatment

et al. 2021

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A genetic predisposition has been identified in 30% of idiopathic pulmonary fibrosis (IPF) cases. Although it is highly probable that the genotype affects the disease susceptibility and course in almost all patients, the specific genotype goes undetected. The aim of the present study was to explore the effects of variants of the genes encoding interleukin-4 (IL-4), mucin 5B (MUC5B), toll interacting protein (TOLLIP), surfactant protein A (SFPTA), transforming growth factor-β (TGF-β) and transporters associated with antigen processing (TAP1 and TAP2) on the course of IPF. A total of 50 patients with IPF were enrolled, and variants of these genes were assessed. Lung function at the time of diagnosis and after 6, 12 and 18 months, and the number of acute exacerbations and deaths in each observation period were measured. ANOVA was used to test the association between gene polymorphisms and the decrease in lung function. There was no significant effect of the gene polymorphisms on the outcomes of patients up to 6 months during the observation period. After 12 months, an effect of an IL-4 single nucleotide polymorphism (SNP) (rs 2070874) on patient outcomes was observed [relative risk (RR) for T allele: 5.6; 95% confidence interval (CI), 0.79-39.0; P=0.053]. The RR of progression in patients with the IL-4 SNP (rs 2243250) and the CT and TT genotypes was 4.3 (95% CI, 1.1-17.5; P=0.046). A total of 18 months after the diagnosis of IPF, an effect of the TOLLIP polymorphism on patient outcome was detected (rs 111521887; risk allele GC; RR: 7.2; 95% CI, 0.97-53.6; P=0.052). Thus, IL-4 and TOLLIP gene polymorphisms may represent disease course-modifying factors, but not drivers of IPF.

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Association of TAP1 and TAP2 polymorphisms with the outcome of persistent HBV infection in a northeast Han Chinese population

Abstract: These results suggested that TAP variants were likely to play a substantial role in different outcomes of persistent HBV infection in the studied population.

Cited by 8 publications

References 26 publications

Acetaldehyde suppresses the display of HBV-MHC class I complexes on HBV-expressing hepatocytes

Acetaldehyde suppresses the display of HBV-MHC class I complexes on HBV-expressing hepatocytes

Association of TAP1 1177A>G and 2090A>G gene polymorphisms with latent tuberculosis infections in sheltered populations, in the metropolitan area of Guadalajara, Mexico: a pilot study

Effect of genotype on the disease course in idiopathic pulmonary fibrosis despite antifibrotic treatment

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