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

Hepatitis B viral replication influences the expression of natural killer cell ligands
Hepatitis B viral replication influences the expression of natural killer cell ligands
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
1108-7471
348-357
Koumbi, Lemonica
0ddc411b-bffc-4d7d-9433-e2409e92d9b9
Pollicino, Teresa
553d091a-81be-4f41-ac16-c7d8b4a06b69
Raimondo, Giovanni
43c72d28-a4b5-41ae-b3c8-1a3bea69db29
Kumar, Naveenta
bc079422-0d86-4dc8-bf27-a5b180d2181d
Karayiannis, Peter
f58f783e-c0d0-4123-9238-5d7702284df2
Khakoo, Salim
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Koumbi, Lemonica
0ddc411b-bffc-4d7d-9433-e2409e92d9b9
Pollicino, Teresa
553d091a-81be-4f41-ac16-c7d8b4a06b69
Raimondo, Giovanni
43c72d28-a4b5-41ae-b3c8-1a3bea69db29
Kumar, Naveenta
bc079422-0d86-4dc8-bf27-a5b180d2181d
Karayiannis, Peter
f58f783e-c0d0-4123-9238-5d7702284df2
Khakoo, Salim
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273

Koumbi, Lemonica, Pollicino, Teresa, Raimondo, Giovanni, Kumar, Naveenta, Karayiannis, Peter and Khakoo, Salim (2016) Hepatitis B viral replication influences the expression of natural killer cell ligands. Annals of Gastroenterology, 29, 348-357. (doi:10.20524/aog.2016.0036).

Record type: Article

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

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Accepted/In Press date: 28 March 2016
e-pub ahead of print date: 25 April 2016
Published date: 25 April 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 398167
URI: https://eprints.soton.ac.uk/id/eprint/398167
ISSN: 1108-7471
PURE UUID: 25d381c0-6951-430b-a7b4-8a2e82d8068b

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Date deposited: 21 Jul 2016 08:38
Last modified: 09 Dec 2019 19:32

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