Naturally Occurring Mutations of Hepatitis B virus and Hepatitis C Virus in Korean Chronic Patients by Distinct CD4 T Cell Responses

Hong Kim; Bum-Joon Kim

doi:10.4167/jbv.2014.44.1.37

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Kim and Kim: Naturally Occurring Mutations of Hepatitis B virus and Hepatitis C Virus in Korean Chronic Patients by Distinct CD4 T Cell Responses

Review Article

J Bacteriol Virol 2014;44(1):37-43.

Published online: 9 February 2014

DOI: https://doi.org/10.4167/jbv.2014.44.1.37

Naturally Occurring Mutations of Hepatitis B virus and Hepatitis C Virus in Korean Chronic Patients by Distinct CD4 T Cell Responses

Hong Kim, Bum-Joon Kim^*

Department of Microbiology and Immunology, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University Seoul, Korea

^*Corresponding author: Bum-Joon Kim. Department of Microbiology and Immunology, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea. Phone: +82-2-740-8316, Fax: +82-2-743-0881, e-mail: kbumjoon@snu.ac.kr

^** This research was supported by grant number 0420100830 from the SNUH Research Fund in 2010.

Received 10 February 201421 February 2014 Accepted 24 February 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most common causes of chronic liver disease worldwide. The host immune pressure against hepatitis viruses during the chronic infection has led to mutations in their coding genes, which could play a pivotal role in the clinical outcomes of chronic patients. Our recent molecular epidemiologic studies regarding the HBV precore/core (preC/C) regions and HCV nonstructural 5B (NS5B) protein suggest the presence of distinct CD4 T cell immune pressure against HBV and HCV in Korean chronic patients. However, induced HBV and HCV mutations seem to exert an opposite effect on Korean chronic hepatitis B (CHB) and chronic hepatitis C (CHC) patients, respectively. On the basis of two of our recent papers, we focused in this review on the relationships between the mutation patterns of HBV preC/C and HCV NS5B, which were presumed to be caused by distinct CD4 T cell pressure in the Korean population and their effect on the clinical outcomes and liver disease progression of CHB and CHC patients.

Keywords: Hepatitis B virus (HBV), Hepatitis C virus (HCV), Mutations, Precore/core (preC/C), Nonstructural 5B (NS5B)

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Figure 1.

Six types of HBV preC/C mutations related to the severity of liver diseases in Korean chronic patients. The types of mutations within the region of MHC II-restricted T-cell epitopes are marked. For comparison between patients with HCC and other disease types, preC/C mutations of 35 HCC patients and 35 patients with other types of liver diseases (27 of chronic hepatitis and 8 patients of liver cirrhosis) were analyzed. To analyze the mutation patterns and their frequencies of deletions and insertions in the entire preC/C region, a nested PCR protocol was used. First-round PCR was performed using the sense primer CoreF1 (59-AAC GAC CGA CCT TGA GGC ATA CTT-39) and the antisense primer CoreR1 (59-ATT TGG TAA GGT TAG GAT AGA A-39) to yield a 1,017 bp amplicon between 1,682 nt to 2,698 nt of the HBV genome. Second-round PCR was performed using the sense primer CoreF2 (59-GAG TTG GGG GAG GAG ATT AGG TTA-39) and the antisense primer [11].

Figure 2.

Mutation frequency at the 309, 333, 338 and 355 codons related to SVR and ETR in the NS5B region. The 166 quasispecies clones of HCV NS5B from 15 genotype 1b infected Korean patients were analyzed. For quasispecies analysis, the nested PCR protocol was performed. The first round of amplification was carried out using the sense primer A1b (O/S) (accession no. M62321, positions 8113-8135 59 – CTGACRACTAGCTGYGGTAAYAC – 39) and the antisense primer F1b (O/A) (positions 8678-8699, 59 – CCTGGAGAGTAACTRTGGAGTG – 39). The second round of amplification was carried out using the sense primer B1b (I/S) (positions 8181-8205, 59 – GCTCCRGGACTGCACSATGCTCGTG – 39) and the antisense primer E1b (I/A) (positions 8654-8675, 59 – AATGCGCTRAGRCCATGGAGTC – 39) to amplify 495 bp of the GT-1b NS5B region [28].

Figure 3.

The presence of distinct CD4 T cell response in Korean patients may lead to opposite clinical outcomes in CHB and CHC Korean patients. The difference in clinical outcomes by viral mutations via distinct immune pressure between patients with CHB and CHC may be mainly due to the difference between HBV and HCV in the infections of Korean chronic patients, such as the vertical infection from mother to child versus horizontal infection.

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