Hepatitis B viral replication influences the expression of natural killer cell ligands

Lemonica Koumbi, Teresa Pollicino, Giovanni Raimondo, Naveenta Kumar, Peter Karayiannis, Salim I. Khakoo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors. HBV may circumvent host antiviral immunity via the regulation of NK receptors and their ligands. We investigated the effect of viral replication and HBeAg mutations on NK mediators expression in the livers of chronic HBV (CHB) patients and in cell cultures. Methods HBV monomers bearing hotspot mutations in the basal core promoter and precore region were transfected into HepG2 cells using a plasmid-free assay. Serum viremia and liver HBV RNA were measured in 19 CHB patients. The expression of HBV RNA and of NKG2D ligands, B7H6, DNAX accessory molecule-1, lectin-like transcript 1 (LLT1), LFA-1 and TRAIL was measured in the livers of CHB patients and transfected cells. Results In general, high HBV replication in CHB patients and cell lines upregulated the mRNA of all NK cell ligands and particularly the inhibitory NK cell ligand, LLT1. The exception was the NKG2D ligand, MICA, that was significantly decreased in patients with high serum viremia and intrahepatic HBV RNA levels. Conclusions HBV replication has differential effects on NK cell ligands suggesting a potential escape mechanisms through up-regulation of LLT1 and down-regulation of MICA. A general trend towards upregulating NK cell ligands can be counteracted by decreasing MICA and hence weakening NK surveillance.

Original languageEnglish
Pages (from-to)348-357
Number of pages10
JournalAnnals of Gastroenterology
Volume29
Issue number3
DOIs
Publication statusPublished - 2016

Fingerprint

Hepatitis B
Hepatitis B virus
Natural Killer Cells
Ligands
Lectins
Liver
Viremia
RNA
Virus Replication
Lymphocyte Function-Associated Antigen-1
Mutation
Hepatitis B e Antigens
Chronic Hepatitis B
Hep G2 Cells
Serum
Genetic Promoter Regions
Antiviral Agents
Immunity
Plasmids
Up-Regulation

Keywords

  • Hepatitis B virus
  • LLT1
  • Mutations
  • NK cells
  • NKG2D
  • Precore
  • Viral replication
  • Virus

Cite this

Koumbi, Lemonica ; Pollicino, Teresa ; Raimondo, Giovanni ; Kumar, Naveenta ; Karayiannis, Peter ; Khakoo, Salim I. / Hepatitis B viral replication influences the expression of natural killer cell ligands. In: Annals of Gastroenterology. 2016 ; Vol. 29, No. 3. pp. 348-357.
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Hepatitis B viral replication influences the expression of natural killer cell ligands. / Koumbi, Lemonica; Pollicino, Teresa; Raimondo, Giovanni; Kumar, Naveenta; Karayiannis, Peter; Khakoo, Salim I.

In: Annals of Gastroenterology, Vol. 29, No. 3, 2016, p. 348-357.

Research output: Contribution to journalArticle

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T1 - Hepatitis B viral replication influences the expression of natural killer cell ligands

AU - Koumbi, Lemonica

AU - Pollicino, Teresa

AU - Raimondo, Giovanni

AU - Kumar, Naveenta

AU - Karayiannis, Peter

AU - Khakoo, Salim I.

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N2 - Background Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors. HBV may circumvent host antiviral immunity via the regulation of NK receptors and their ligands. We investigated the effect of viral replication and HBeAg mutations on NK mediators expression in the livers of chronic HBV (CHB) patients and in cell cultures. Methods HBV monomers bearing hotspot mutations in the basal core promoter and precore region were transfected into HepG2 cells using a plasmid-free assay. Serum viremia and liver HBV RNA were measured in 19 CHB patients. The expression of HBV RNA and of NKG2D ligands, B7H6, DNAX accessory molecule-1, lectin-like transcript 1 (LLT1), LFA-1 and TRAIL was measured in the livers of CHB patients and transfected cells. Results In general, high HBV replication in CHB patients and cell lines upregulated the mRNA of all NK cell ligands and particularly the inhibitory NK cell ligand, LLT1. The exception was the NKG2D ligand, MICA, that was significantly decreased in patients with high serum viremia and intrahepatic HBV RNA levels. Conclusions HBV replication has differential effects on NK cell ligands suggesting a potential escape mechanisms through up-regulation of LLT1 and down-regulation of MICA. A general trend towards upregulating NK cell ligands can be counteracted by decreasing MICA and hence weakening NK surveillance.

AB - Background Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors. HBV may circumvent host antiviral immunity via the regulation of NK receptors and their ligands. We investigated the effect of viral replication and HBeAg mutations on NK mediators expression in the livers of chronic HBV (CHB) patients and in cell cultures. Methods HBV monomers bearing hotspot mutations in the basal core promoter and precore region were transfected into HepG2 cells using a plasmid-free assay. Serum viremia and liver HBV RNA were measured in 19 CHB patients. The expression of HBV RNA and of NKG2D ligands, B7H6, DNAX accessory molecule-1, lectin-like transcript 1 (LLT1), LFA-1 and TRAIL was measured in the livers of CHB patients and transfected cells. Results In general, high HBV replication in CHB patients and cell lines upregulated the mRNA of all NK cell ligands and particularly the inhibitory NK cell ligand, LLT1. The exception was the NKG2D ligand, MICA, that was significantly decreased in patients with high serum viremia and intrahepatic HBV RNA levels. Conclusions HBV replication has differential effects on NK cell ligands suggesting a potential escape mechanisms through up-regulation of LLT1 and down-regulation of MICA. A general trend towards upregulating NK cell ligands can be counteracted by decreasing MICA and hence weakening NK surveillance.

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