Genetic Analysis of Hepatitis A Virus Isolated from Korea

Kyung-Ok Lee; Su-Jin Jeong; Hye-Soon Seong; Kyung-Tae Kim; Yoo-Sung Hwang; Gee-Young Kim; Sun-Hwa Lee

doi:10.4167/jbv.2009.39.3.165

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Lee, Jeong, Seong, Kim, Hwang, Kim, and Lee: Genetic Analysis of Hepatitis A Virus Isolated from Korea

Original Article

J Bacteriol Virol 2009;39(3):165-171.

Published online: 18 January 2009

DOI: https://doi.org/10.4167/jbv.2009.39.3.165

Genetic Analysis of Hepatitis A Virus Isolated from Korea

Kyung-Ok Lee, Su-Jin Jeong, Hye-Soon Seong, Kyung-Tae Kim, Yoo-Sung Hwang, Gee-Young Kim, Sun-Hwa Lee

Genome Research Center, Neodin Medical Institute, Seoul, Korea

^∗Corresponding author: Kyung Ok Lee, Ph.D. Genome Research Center, Neodin Medical Institute, #2-3, Yongdap-Dong, Sungdong-gu, Seoul, 133-847, Korea. Phone: +82-2-2244-6500, Fax: +82-2-2212-1307, e-mail: grace97284@yahoo.co.kr

Revised 16 June 200915 July 2009 Accepted 21 July 2009

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 A virus (HAV) is one of the most important causes of acute infectious hepatitis. The aim of this study was to determine the genotypes of HAV that have been circulating in Koreans. A total of 76 sera referred to our institute for HAV genotyping from 11 Korean provinces were used for this study. Those samples were diagnosed by positive of IgM anti-HAV. HAV RNA was extracted from 150 μl of serum, and reverse transcription PCR-sequencing was used to detect and characterize HAV RNA. Primer pairs from the VP1/2A region of the HAV were used for amplification and sequencing. HAV RNA was found in 64.5% (n = 49) of the 76 patient sera with acute hepatitis A. Forty-seven strains were genotype IIIA in a total of 49 isolated strains (95.9%, 47/49); only two strains belonged to genotype IA (4.1%, 2/49). Thirty eight genotype IIIA isolates were 100% identical to consensus amino acid sequences of the reference strain AJ299467. The amino acid change of L772F was found in two IIIA strains; other IIIA isolates showed one amino acid change. Amino acid of genotype IA was compared to reference strain L20541. K801R was found in 1 strain and Q810S in both strains. The amino acid change of K801R was the first report in Koreans. Until recently HAV genotype IA has been reported as a major circulating HAV genotype in Koreans. In the present study, the predominant HAV strain in Koreans seemed to be HAV genotype IIIA.

Keywords: Hepatitis A, Genotype

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Figure 1.

Neighbor-joining phylogenetic tree nucleotide sequences in the VP1/P2A region of H AV isolates in Korea. The tree includes reference strains L20541, L07676, L20553, L07722 and L07717 in genotype IA, L07703 in genotype IB, L07729 in genotype IIB, L07725, L0766 and AJ2994678 in genotype IIIA, L205328 in genotype IIIB, L077328 in genotype IV, L07731 in genotype VI. The horizontal bar at the bottom represents a genetic distance of 0.02.

Figure 2.

Comparison of the predicted amino acid sequences of the VP1/VP2 junction region of HAV. The consensus amino acid sequences of AJ299467 for HAV genotype IIIA and L20541 for HAV genotype IA are shown on the top line of (A) and (B), respectively. “–” indicates conserved amino acid; differences are shown by the appropriate single letter amino acid code. The numbers above the consensus amino acid sequence indicate the predicted amino acid number from the start of HAV full amino acid. The numbers of the right ends indicate the number of HAV strains we found in the present study.

Table 1.

Molecular characters and nucleic acid sequences homologies of 49 strains at the VP1/2A region of hepatitis A Virus (HAV) in Korean HAV isolates compared to reference strains, AJ299467 and L20541 for genotype IIIA and IA, respectively

Isolate	Identity (%)	Genotype	Province	Year
ND91610	99.22	3A	Chonan	2007
ND91611	98.83	3A	Inchon	2007
ND91612	99.22	3A	Seoul	2007
ND91613	99.61	3A	Seoul	2007
ND91614	99.22	3A	Suwon	2007
ND91616	99.61	3A	Anyang	2007
ND91618	99.61	3A	Inchon	2007
ND91620	98.44	3A	Seoul	2007
ND91623	96.50	3A	Kwangju	2007
ND91624	98.83	3A	Jonju	2007
ND92401	98.83	3A	Anyang	2008
ND92403	98.44	3A	Seoul	2008
ND92404	98.83	3A	Suwon	2008
ND92406	98.83	3A	Anyang	2008
ND92407	99.61	3A	Wonju	2008
ND92408	99.61	3A	Seoul	2008
ND92427	99.61	3A	Anyang	2008
ND92428	98.83	3A	Seoul	2008
ND92430	99.22	3A	Seoul	2008
ND92432	99.22	3A	Kwangju	2008
ND92433	99.22	3A	Anyang	2008
ND92435	99.61	3A	Seoul	2008
ND92437	99.61	3A	Kwangju	2008
ND92439	99.61	3A	Seoul	2008
ND92443	100.00	3A	Inchon	2008
ND92444	99.22	3A	Anyang	2008
ND72600	99.22	3A	Chonan	2008
ND72800	98.05	3A	Suwon	2008
ND81200	98.83	3A	Inchon	2008
ND81800	99.61	3A	Seoul	2008
ND82600	98.83	3A	Anyang	2008
ND90400	98.05	3A	Inchon	2008
ND92301	99.22	3A	Inchon	2008
ND92303	100.00	3A	Seoul	2008
ND92305	97.28	3A	Inchon	2008
ND10141	98.83	3A	Inchon	2008
ND10143	99.22	3A	Anyang	2008
ND10144	99.22	3A	Inchon	2008
ND10211	99.61	3A	Anyang	2008
ND91201	99.22	3A	Seoul	2008
ND91203	99.61	3A	Anyang	2008
ND91205	99.61	3A	Seoul	2008
ND91206	99.22	3A	Seoul	2008
ND91207	99.61	3A	Kangleung	2008
ND12312	98.83	3A	Seoul	2008
ND12314	99.22	3A	Wulsan	2008
ND12315	98.44	3A	Seoul	2008
ND91622	96.43	1A	Suwon	2007
ND93000	96.43	1A	Seoul	2008

Table 2.

Amino acid changes of Korean HAV strains in VP1/2A region of HAV from 2007 to 2008

Amino acid position	Genotype	Prototype	Substitution	Number
764	3A	E	K	1
767	3A	M	R	1
769	3A	R	K	1
772	3A	L	F	2
789	3A	K	R	1
793	3A	H	R	1
809	3A	K	N	1
820	3A	S	P	1
825	3A	P	S	1
830	3A	I	L	1
836	3A	Q	R	1
838	3A	K	E	1
801	1A	K	R	1
810	1A	Q	S	2

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Amino acid position	Genotype	Prototype	Substitution	Number
764	3A	E	K	1
767	3A	M	R	1
769	3A	R	K	1
772	3A	L	F	2
789	3A	K	R	1
793	3A	H	R	1
809	3A	K	N	1
820	3A	S	P	1
825	3A	P	S	1
830	3A	I	L	1
836	3A	Q	R	1
838	3A	K	E	1
801	1A	K	R	1
810	1A	Q	S	2

Amino acid position	Genotype	Prototype	Substitution	Number
764	3A	E	K	1
767	3A	M	R	1
769	3A	R	K	1
772	3A	L	F	2
789	3A	K	R	1
793	3A	H	R	1
809	3A	K	N	1
820	3A	S	P	1
825	3A	P	S	1
830	3A	I	L	1
836	3A	Q	R	1
838	3A	K	E	1
801	1A	K	R	1
810	1A	Q	S	2

Amino acid position	Genotype	Prototype	Substitution	Number
764	3A	E	K	1
767	3A	M	R	1
769	3A	R	K	1
772	3A	L	F	2
789	3A	K	R	1
793	3A	H	R	1
809	3A	K	N	1
820	3A	S	P	1
825	3A	P	S	1
830	3A	I	L	1
836	3A	Q	R	1
838	3A	K	E	1
801	1A	K	R	1
810	1A	Q	S	2