Warning: fopen(/home/virtual/pediatrics/journal/upload/ip_log/ip_log_2024-04.txt) [function.fopen]: failed to open stream: Permission denied in /home/virtual/pediatrics/journal/ip_info/view_data.php on line 82

Warning: fwrite(): supplied argument is not a valid stream resource in /home/virtual/pediatrics/journal/ip_info/view_data.php on line 83
Prevalence of rotavirus genotypes in South Korea in 1989-2009: implications for a nationwide rotavirus vaccine program

Volume 56(11); November

< Previous     Next >

Article Contents

Clin Exp Pediatr > Volume 56(11); 2013
Than and Kim: Prevalence of rotavirus genotypes in South Korea in 1989-2009: implications for a nationwide rotavirus vaccine program


The epidemiology of human group A rotavirus was analyzed by examining genotypic data acquired from 1989 to 2009 in South Korea. This information was derived from all the available published articles on rotavirus studies in South Korea, retrieved from both the PubMed and KoreaMed databases. Four common G types (G1, G2, G3, and G4) and three common P types (P[8], P[4], and P[6]) accounted for approximately 93% and 99% of the rotavirus reports, respectively. The G9 type was frequently detected after 2000, and because of this prevalence, it is considered to be the fifth most important G type rotavirus after the G1.G4 genotypes. Less common G types of the virus such as G12, G11, and G10 were detected in some geographic settings, and it is important to consider the context of these subtypes and their epidemiological significance. The P[9] virus genotype was observed in the study and has been discussed in many other studies; however, the P[3], P[10] and P[25] genotypes were rarely detected in the epidemiological research. In general, the distributions of the G and P genotypes showed temporal and geographical fluctuations, and a nationwide rotavirus vaccine program that targeted these genotypes demonstrated effectiveness in protecting against the circulating rotavirus strains. However, further analysis is needed to determine the true long-term effectiveness of these vaccines; the analysis should also consider the unexpected effects of vaccinations, such as vaccine-induced diseases, herd immunity, and changes in host susceptibilities.


Rotavirus is the most common causal agent of acute diarrhea among children worldwide and is transmitted between individuals via the fecal-oral route1). Approximately half a million children under the age of five die from rotavirus infections every year2). Most of these children reside in low-income countries in Africa and Asia where access to safe water, sanitation, and medical care is often limited3).
Rotavirus, a member of the Reoviridae family, is classified into eight groups or species named A to H4). The viral genome consists of 12 segments of double-stranded RNA, which encode six structural proteins (VP1-VP4, VP6, and VP7) and six nonstructural proteins (NSP1-NSP6)5). The outer capsid comprises two proteins, the glycoprotein VP7 and the protease-sensitive VP4, which define the G and P genotypes, respectively, and relate to host specificity, virulence, and protective immunity6).
Rotavirus, when diagnosed in the clinical setting, cannot be distinguished from other forms of acute gastroenteritis caused by other microorganisms. Rotavirus infection can be accurately diagnosed by performing a rapid antigen detection of rotavirus in stool samples. Commercially available assays have been developed to detect rotaviruses in clinical samples, including electron microscopy (EM)7), virus culture8), enzyme immunoassay (EIA)9), latex agglutination (LA) assay10), polyacrylamide gel electrophoresis (PAGE)11), dot-blot hybridization assay12), and reverse transcription polymerase chain reaction (RT-PCR)13). Currently, the EIA and RT-PCR methods are the most popular assays for detecting, serotyping, and genotyping infectious rotavirus strains.
In South Korea, rotavirus is the most common cause of acute diarrhea in young children, particularly during the winter months14). Studies on the etiology of childhood diarrhea have shown that rotavirus is the most frequently diagnosed gastroenteritis agent detected in stool specimens obtained from Korean children hospitalized with acute diarrhea, accounting for 41.3-68% of all cases of gastroenteritis15-18).
The purpose of this study was to identify the distributions of G and P rotavirus serotypes on the basis of data collected on children hospitalized with rotavirus-related diarrhea in South Korea between 1989 and 2009. In addition, this review study discusses the genetic and antigenic diversity of Korean rotavirus strains that occur over two decades and which may indicate future trends of circulating rotavirus genotypes. The study data also address information about the control, estimation, and development of a nationwide rotavirus vaccine campaign in Korea.

Materials and methods

The study data were collected through two independent academic article searches of the MEDLINE database. The first search retrieved published studies from the PubMed-NCBI database (http://www.ncbi.nlm.nih.gov). This search used the terms "human," "rotavirus," and "Korea." The second search, which retrieved published articles from the KoreaMed database (http://koreamed.org/SearchBasic.php), used the terms "rotavirus" and "human." Both searches focused on hospitalized children and outpatients who had been hospitalized with acute gastroenteritis.
The genetic sequences of the G and P rotavirus genotypes were obtained from NCBI to create phylogenetic trees for analyzing the genetic diversity of the South Korean rotavirus strains (Supplementary Table 1). The phylogenetic trees were constructed using neighbor-joining algorithms19) from the Phylip package20). Evolutionary distances for the neighbor-joining analysis were based on the model described by Jukes and Cantor21). Tree topology was evaluated using the bootstrap resampling method with 1,000 replicates of the neighbor-joining dataset with the SEQBOOT and CONSENSE programs from the Phylip package.

Summary of rotavirus diagnostic assays

There are several differences in the clinical manifestations and epidemiologic patterns of rotaviral gastroenteritis and other forms of acute gastroenteritis22). However, a rotaviral infection is difficult to diagnose and cannot be identified solely on the basis of symptoms of gastroenteritis. An accurate rotavirus diagnosis requires routine laboratory confirmation such as the detection of virus or viral antigen or demonstration of a serologic response5). Currently, numerous assays have been developed to detect rotaviruses in clinical samples.

1. Electron microscopy

EM visualization is highly specific for rotavirus detection because these viruses have a distinctive morphology with a double-shelled capsid7,23-25). However, the experience and equipment required for an EM diagnosis are labor intensive, which can limit the routine detection of rotavirus for large numbers of clinical specimens. In addition, EM cannot distinguish between rotaviruses of different groups and serotypes.

2. Virus culture

It is possible to isolate rotavirus from clinical specimens and to grow the virus in cell culture with reasonable efficiency8). This method of viral culture has been reported to be approximately 75% as efficient as antigen detection test procedures8,26,27).

3. Enzyme immunoassay

EIA is the preferred identification method in many laboratories because it is highly sensitive, specific, and adaptable to large sample volumes, and it does not require specialized equipment9,23,28). Additionally, EIAs allow VP6 subgroup or VP7 serotype determination because this technique uses serotype-specific monoclonal antibodies29,30).

4. Latex agglutination tests

LA tests are also used to detect rotaviruses. These tests utilize latex particles coated with antirotavirus antibodies against rotavirus antigens10). An LA test is suitable for application as a simple clinical diagnostic test and can be used as an alternative to EIA31).

5. Polyacrylamide gel electrophoresis

The PAGE technique is used to determine the electrophoretic patterns of the rotavirus dsRNA11,32). The viral dsRNA is first extracted and then analyzed by electrophoresis on a polyacrylamide gel, followed by silver staining. The silver staining technique allows the rotavirus to be identified on the basis of the dsRNA pattern, which can be displayed as either a "long" or a "short" electropherotype33).

6. Dot-blot hybridization assay

The dot-blot hybridization assay was developed on the basis of in situ hybridization of labeled rotavirus ssRNA transcripts. These transcripts adhere to heat-denatured rotavirus RNA immobilized on a nitrocellulose membrane. This dot-blot technique has been found to be 10- to 100-fold more sensitive than a confirmatory enzyme-linked immunosorbent assay (ELISA)12,34,35).

7. Reverse transcription polymerase chain reaction

RT-PCR was developed to improve identification of rotaviruses and is based on the amplification of rotavirus RNA13). This technique is theoretically much more sensitive than the ELISA, PAGE, and EM techniques for detecting rotaviruses in different clinical specimens as well as environmental samples36). RT-PCR has significantly reduced the incidence of rotavirus nontypeable strains, which are difficult to identify with less sensitive techniques. Recently, a combination of EIA and RT-PCR was used for detecting, serotyping, and genotyping the infectious rotavirus strains37).

Diagnostic assay detection of rotavirus in South Korea

The majority of previous studies in South Korea have used ELISA to determine rotavirus serotypes by using either VP6- or VP7-specific monoclonal antibodies for G1, 2, 3, and 4 serotypes14,16,38-40). However, the sensitivity and specificity of the ELISA tests are different between commercial ELISA kits. In recent years, with the application of RT-PCR, the incidence rates of nontypeable strains have drastically decreased. RT-PCR was initially used to determine the serotype of rotavirus after a positive ELISA test indicated rotavirus as the causal agent. In addition, previous studies have applied a PAGE assay technique, although this application was only used to characterize detected strains41-43).

Prevalence of G and P genotypes in South Korea

A study on the worldwide G and P rotavirus genotype distributions has indicated that at least 27 G and 35 P genotypes have been reported to date44). Epidemiological studies have shown that of these genotypes, five G (G1-G4, and G9) and three P (P[4], P[6], and P[8]) genotypes are the major genotypes associated with global human rotavirus infections45).

1. G1-G4 genotypes

G1, G2, G3, and G4 are major G genotypes that account for more than 93% of all human rotavirus infections in South Korea (Table 1, Fig. 1). The predominance of each genotype depends on the specific time period and geographic area of viral infections. Prior to 2000, G1 was the predominant genotype14,16,46,47), and studies have indicated that this genotype was predominant mostly between 2004 and 200948-51). The G2 and G3 genotypes were the predominant genotypes during the 2000-2001 and 2003-2005 rotavirus seasons, respectively43,52). Another study has indicated that the G4 genotype was predominant during the 2002-2003 and 2007-2008 seasons41,53). The incidence of the G2, G3, and G4 genotypes generally decreased after the introduction of rotavirus vaccines, whereas the incidence of the G1 genotype slightly increased (Fig. 1). Genetic analysis revealed that genetic variation occurred over time despite the lack of available gene sequence data for the specific South Korean genotypes41,42,54,55). Phylogenetic analysis of the G1 genotype indicated that the G1 strains were clustered in lineage IV, lineage II, and mostly in lineage I and displayed distinctions from the G1 Wa prototype strain, which belongs to lineage III (Fig. 2A)42,54,55). Thirteen available Korean G2 strains were analyzed during the 2000-2001 and 2007-2009 seasons47,54). According to the analyses, 10 strains were clustered into lineage V and three other strains were clustered into lineage IV (Fig. 2A). Genetic analysis of the G3 and G4 genotypes showed that these strains were conserved and clustered into lineages III and Ie, respectively (Fig. 2A)41,54).

2. P[8], P[4], and P[6] genotypes

P[8], P[4], and P[6] are the major P genotypes, and these strains account for approximately 99% of all human rotavirus infections occurring in South Korea (Table 1, Fig. 1). P[8] was the most prevalent genotype, and studies report that this genotype constituted over one-half of all P genotypes identified in many parts of Korea during the study period46,48-53,56). P[6] and P[4] were the second and third most common P genotypes detected, respectively. Similarly, some additional studies show that the P[6] and P[4] genotypes were predominant during specific time periods and in particular geographic areas41,43,52,53). Phylogenetic analysis of the P[8] genotype revealed that these strains clustered into lineage IV and primarily lineage III (Fig. 2B)54,57). Phylogenetic analysis of the P[6] and P[4] genotypes revealed that these strains clustered into lineages V and I, respectively (Fig. 2B).

Clinical significance of unusual G genotypes in South Korea

1. G9 genotype

G9 is known to be the .fth most common genotype, after the G1-G4 genotypes, currently circulating in the human population. The first G9 rotavirus, WI61, was detected in children in the USA in 198358). After this point in time, G9 strains have been widely reported as the causative agents of diarrhea in children and have been recognized in many countries as one of the most widespread and emerging genotypes57). In South Korea, the first G9 strain was detected during the 2000-2001 rotavirus season43). Since then, G9 strains have been detected over consecutive seasons across the country (Table 1). The G9 strain was identified primarily in rural health care centers, and this genotype was found to be responsible for 7.4% to 39% of rural infections51-54,56,59); however, the rate of infection was much lower, only 1% to 3%, in urban hospitals41,48-50,60). G9 genotype detection generally improved after the introduction of rotavirus vaccines (Fig. 1). The low detection rate of G9 strains may be owing to the fact that the current vaccine formulations do not include the G9 antigen.
Currently, six lineages and 11 sublineages of the VP7 gene of G9 rotaviruses have been described in the research literature. A sequence analysis of the VP7 gene of various Korean G9 isolates demonstrated that the recent Korean G9 isolates belong to lineage III, within sublineage d, which also includes other contemporary G9 strains that are prevalent throughout the world (Fig. 2A). The recent increase in the incidence of global G9 human rotavirus infections indicates that type G9 has established itself as a globally common rotavirus G serotype of clinical importance45). Phylogenetic analysis of all 11 gene sequences of the three Korean G9P[8] strains revealed that these strains belonged to genogroup I of the Wa-like genotype constellation, which is one of the two main genotype constellations known to occur among epidemiologically important widespread human rotavirus A strains61).

2. G12 genotype

The first G12 rotavirus, L26, was detected in the Philippines in 19879). Currently, G12 genotypes are classified into four genetic lineages, I to IV62). In South Korea, the G12 genotype was first detected during the 2002-2003 season53). These strains were then intermittently detected in subsequent studies between 2004 and 200948,50,54). Sequence analyses of G12 genotypes in Korea are currently available for four strains (CAU195, CAU214, Seoul-553, and Seoul-681)48,54). These four Korean G12 strains are clustered into lineage III and show high sequence identity with strains isolated in Thailand, Germany, and the United States, which suggests that the Korean G12 strains are closely related to the recently reported G12 strains that emerged worldwide (Fig. 2A)54,63). Phylogenetic analysis of all 11 gene sequences revealed that these genotypes belonged to genogroup I of the Wa-like genotype constellation64). These results suggest that G12 genotypes not only are persistent but also may have adapted and evolved in the South Korean population.

3. G10 and G11 genotypes

Research analyses show that G10 and G11 rotavirus strains have rarely been detected in South Korea. Until now, only one G10 strain has been detected in Korea, and this occurred during the 2004-2005 season60). G11 strain analysis indicated that this strain was initially detected and characterized in the 2005-2006 season65) and was identified again during the 2008-2009 season49). However, additional studies are needed to investigate the importance and distribution of these rotavirus strains in the Korean population because only a few studies that specifically examine these G10 and G11 rotavirus strains have been conducted as yet (Table 1).

Clinical significance of unusual P genotypes in South Korea

1. P[9] genotype

The P[9] genotype is frequently detected in cats66), and the first P[9] human rotavirus, the K8 strain with G1 speci.city, was isolated from a 14-year-old schoolboy in Hokkaido, Japan in 197767). Although P[9] genotypes have been detected in most of the rotavirus surveillance studies in South Korea, there has been no significant emergence of P[9] genotypes in the Korean population43,48-51,53,59,60). Research has indicated that the majority of the P[9] strains carry G1, G2, and G3 specificity, except for a few isolates that were identified to have both G9 and G12 specificity48,51,53). Currently, no studies have focused on this genotype; therefore, further analysis of the circulating Korean P[9] genotypes is needed to understand their origin, genetic variation, and potential impact on the human population (Table 1).

2. P[3], P[10], and P[25] genotypes

To date, only one P[3] genotype and one P[25] genotype (unpublished data, KC140588) were detected during the 2003-2005 and 2011-2012 rotavirus seasons, respectively52). A total of five P[10] strains were detected in South Korea during three different rotavirus seasons43,51,60). However, the genetic profiles of the P[3] and P[10] genotypes have not been analyzed, even though the Korean P[25] genotype was found to be closely related to the P[25] genotypes isolated from Bangladesh (Dhaka6), Nepal (KTM368), and India (CRI10795) (unpublished data) (Fig. 2B). Because of these similarities and the implications for future rotavirus outbreaks, additional analysis of these genotypes is necessary (Table 1).

Prevalence of G and P genotypes and future implications for a nationwide rotavirus vaccine program in South Korea

Surveillance studies of the G and P genotypes in South Korea between 1989 and 2009 have provided important new information about rotavirus strain diversity. These studies have shown that there are six broad types of rotavirus strains, i.e., G1.G4, G9, and P[8]. These results are in agreement with the worldwide trend of the G and P rotavirus genotypes, in which a total of five G and P combinations (G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8]) account for approximately 90% of all human rotavirus infections68).
Recently, two effective rotavirus vaccines have become available. The first vaccine, Rotarix (GlaxoSmithKline Biologicals, Rixensart, Belgium), is based on an attenuated G1P[8] rotavirus, whereas the other vaccine, RotaTeq (Merck & Co., Whitehouse Station, NJ, USA), is a human-bovine reassortant vaccine that contains the genotypes G1-G4 and P[8]. Rotarix has been approved in 90 countries worldwide and has shown an 80.5% efficacy against non-G1P[8] genotypes, including the G9P[8] genotype69-71). RotaTeq has been filed in more than 100 countries and has been reported to reduce hospital admission and emergency department visits by 94.5% after the third dose72). These two vaccines were introduced in South Korea in September 2007 and July 2008, respectively, and have been shown to be effective, safe, and economical through a nationwide rotavirus vaccination campaign73-75). In addition, the introduction of the RotaTeq vaccine in a three-dose regimen has reduced the rate of symptomatic rotavirus infections in South Korean infants by approximately 63.2% over a 5-year period73).


Rotavirus is the most common causal agent of acute diarrhea among children worldwide and is the most common causal agent of gastroenteritis in infants and young South Korean children. Currently, many assays are available for virus detection in clinical samples. The most common tests used for detection are the EIA and RT-PCR tests, which are used for detecting, serotyping, and genotyping virus infections. This review analyzed the epidemiology of G and P rotavirus genotypes on the basis of data between 1989 and 2009. All the available published articles on rotavirus studies in South Korea were retrieved from either the PubMed or KoreaMed databases.
The review analysis showed that the G genotypes G1-G4 were consistent and predominant, and that G9 strains were frequently detected. Other G genotypes such as G12, G11, and G10 were detected in some geographic settings; however, it was difficult to estimate the epidemiological importance of these genotypes owing to limited analyses (Table 1). With regard to the P genotypes, P[8] was found to be responsible for more than 53% of the infections, followed by P[6] and P[4] at 24% and 20%, respectively (Table 1). P[9] genotypes were reported in numerous studies, whereas P[3], P[10], and P[25] genotypes were rarely detected (Table 1). In general, the distributions of the G and P genotypes were found to be related to temporal and geographical fluctuations.
This study also addressed the application and effectiveness of rotavirus vaccines. However, further analysis is needed to determine the effectiveness and impact of these vaccines on the current and future trends of rotavirus genotypes. In addition, further characterization of the unexpected effects of rotavirus vaccines, such as vaccine-induced diseases, herd immunity, and changes in host susceptibilities, is also needed.


This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2A10012148).

Conflicts of interest

The authors have no con.icts of interest to disclose.

Supplementary materials

Supplementary Table 1 can be found via http://kjp.or.kr/upload/2013600040-supp.pdf.

Supplementary Table 1

Korean rotavirus G and P genotypes used in this study


1. Cortese MM, Parashar UD. Centers for Disease Control and Prevention (CDC). Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2009;58(RR-2): 1–25.

2. Parashar UD, Burton A, Lanata C, Boschi-Pinto C, Shibuya K, Steele D, et al. Global mortality associated with rotavirus disease among children in 2004. J Infect Dis 2009;200(Suppl 1): S9–S15.
crossref pmid
3. Patel MM, Steele D, Gentsch JR, Wecker J, Glass RI, Parashar UD. Real-world impact of rotavirus vaccination. Pediatr Infect Dis J 2011;30(1 Suppl): S1–S5.
crossref pmid
4. Matthijnssens J, Otto PH, Ciarlet M, Desselberger U, Van Ranst M, Johne R. VP6-sequence-based cutoff values as a criterion for rotavirus species demarcation. Arch Virol 2012;157:1177–1182.
crossref pmid
5. Estes MK. Rotaviruses. Knipe DM, Howley PM, Griffin DE, Martin MA, editors. Fields virology. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2007;:1917–1974.

6. Estes MK, Cohen J. Rotavirus gene structure and function. Microbiol Rev 1989;53:410–449.
crossref pmid pmc
7. Bishop RF, Davidson GP, Holmes IH, Ruck BJ. Detection of a new virus by electron microscopy of faecal extracts from children with acute gastroenteritis. Lancet 1974;1:149–151.
8. Hasegawa A, Matsuno S, Inouye S, Kono R, Tsurukubo Y, Mukoyama A, et al. Isolation of human rotaviruses in primary cultures of monkey kidney cells. J Clin Microbiol 1982;16:387–390.
crossref pmid pmc
9. Yolken R, Wyatt RG, Kapikian AZ. ELISA for rotavirus. Lancet 1977;2:819

10. Haikala OJ, Kokkonen JO, Leinonen MK, Nurmi T, Mantyjarvi R, Sarkkinen HK. Rapid detection of rotavirus in stool by latex agglutination: comparison with radioimmunoassay and electron microscopy and clinical evaluation of the test. J Med Virol 1983;11:91–97.
crossref pmid
11. Kalica AR, Sereno MM, Wyatt RG, Mebus CA, Chanock RM, Kapikian AZ. Comparison of human and animal rotavirus strains by gel electrophoresis of viral RNA. Virology 1978;87:247–255.
crossref pmid
12. Flores J, Boeggeman E, Purcell RH, Sereno M, Perez I, White L, et al. A dot hybridisation assay for detection of rotavirus. Lancet 1983;1:555–558.
13. Wilde J, Yolken R, Willoughby R, Eiden J. Improved detection of rotavirus shedding by polymerase chain reaction. Lancet 1991;337:323–326.
crossref pmid
14. Seo JK, Sim JG. Overview of rotavirus infections in Korea. Pediatr Int 2000;42:406–410.
crossref pmid
15. Kim KH, Suh IS, Kim JM, Kim CW, Cho YJ. Etiology of childhood diarrhea in Korea. J Clin Microbiol 1989;27:1192–1196.
crossref pmid pmc
16. Kim KH, Yang JM, Joo SI, Cho YG, Glass RI, Cho YJ. Importance of rotavirus and adenovirus types 40 and 41 in acute gastroenteritis in Korean children. J Clin Microbiol 1990;28:2279–2284.
crossref pmid pmc
17. Huh JW, Kim WH, Moon SG, Lee JB, Lim YH. Viral etiology and incidence associated with acute gastroenteritis in a 5-year survey in Gyeonggi province, South Korea. J Clin Virol 2009;44:152–156.
crossref pmid
18. Koh H, Baek SY, Shin JI, Chung KS, Jee YM. Coinfection of viral agents in Korean children with acute watery diarrhea. J Korean Med Sci 2008;23:937–940.
crossref pmid pmc
19. Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 1987;4:406–425.
crossref pmid
20. Felsenstein J. PHYLIP (Phylogeny inference package) version 3.5c. Seattle: Department of Genetics, University of Washington, 1993.

21. Jukes TH, Cantor CR. Evolution of protein molecules: mammalian protein metabolism. New York: Academic Press, 1969;:21–132.

22. Bass ES, Pappano DA, Humiston SG. Rotavirus. Pediatr Rev 2007;28:183–191.
crossref pmid
23. Brandt CD, Kim HW, Rodriguez WJ, Thomas L, Yolken RH, Arrobio JO, et al. Comparison of direct electron microscopy, immune electron microscopy, and rotavirus enzyme-linked immunosorbent assay for detection of gastroenteritis viruses in children. J Clin Microbiol 1981;13:976–981.
crossref pmid pmc
24. Flewett TH, Bryden AS, Davies H. Letter: virus particles in gastroenteritis. Lancet 1973;2:1497

25. Kapikian AZ, Dienstag JL, Purcell RH. Immune electron microscopy as a method for the detection, identification, and characterization of agents not cultivable in an in vitrosystem. Rose NR, Friedman H, editors. Manual of clinical immunology. Washington, DC: American Society for Microbiology, 1976;:467–480.

26. Birch CJ, Rodger SM, Marshall JA, Gust ID. Replication of human rotavirus in cell culture. J Med Virol 1983;11:241–250.
crossref pmid
27. Urasawa S, Urasawa T, Taniguchi K. Three human rotavirus serotypes demonstrated by plaque neutralization of isolated strains. Infect Immun 1982;38:781–784.
crossref pmid pmc
28. Yolken RH, Kim HW, Clem T, Wyatt RG, Kalica AR, Chanock RM, et al. Enzyme-linked immunosorbent assay (ELISA) for detection of human reovirus-like agent of infantile gastroenteritis. Lancet 1977;2:263–267.
29. Taniguchi K, Urasawa T, Morita Y, Greenberg HB, Urasawa S. Direct serotyping of human rotavirus in stools by an enzyme-linked immunosorbent assay using serotype 1-, 2-, 3-, and 4-specific monoclonal antibodies to VP7. J Infect Dis 1987;155:1159–1166.
crossref pmid
30. Greenberg H, McAuliffe V, Valdesuso J, Wyatt R, Flores J, Kalica A, et al. Serological analysis of the subgroup protein of rotavirus, using monoclonal antibodies. Infect Immun 1983;39:91–99.
crossref pmid pmc
31. Sanekata T, Yoshida Y, Okada H. Detection of rotavirus in faeces by latex agglutination. J Immunol Methods 1981;41:377–385.
crossref pmid
32. Espejo RT, Calderon E, Gonzalez N. Distinct reovirus-like agents associated with acute infantile gastroenteritis. J Clin Microbiol 1977;6:502–506.
crossref pmid pmc pdf
33. Matsui SM, Mackow ER, Matsuno S, Paul PS, Greenberg HB. Sequence analysis of gene 11 equivalents from "short" and "super short" strains of rotavirus. J Virol 1990;64:120–124.
crossref pmid pmc
34. Fernandez J, Sandino A, Yudelevich A, Avendano LF, Venegas A, Hinrichsen V, et al. Rotavirus detection by dot blot hybridization assay using a non-radioactive synthetic oligodeoxynucleotide probe. Epidemiol Infect 1992;108:175–184.
crossref pmid pmc
35. Yamakawa K, Nakagomi O. Improved detection of rotavirus RNA in dot-blot hybridization assay by chromatographic extraction and acid denaturation of double-stranded RNA. Mol Cell Probes 1990;4:415–418.
crossref pmid
36. Buesa J, Colomina J, Raga J, Villanueva A, Prat J. Evaluation of reverse transcription and polymerase chain reaction (RT/PCR) for the detection of rotaviruses: applications of the assay. Res Virol 1996;147:353–361.
crossref pmid pmc
37. Bishop RF, Masendycz PJ, Bugg HC, Carlin JB, Barnes GL. Epidemiological patterns of rotaviruses causing severe gastroenteritis in young children throughout Australia from 1993 to 1996. J Clin Microbiol 2001;39:1085–1091.
crossref pmid pmc
38. Kang CM. Clinical, epidemiological, and serological observation on human rotavirus gastroenteritis in infants and children. J Korean Pediatr Soc 1985;28:140–146.

39. Rhee EO, Hwang NJ, Choi YS, Seo SS. Clinical studies of human rotavirus gastroenteritis. J Korean Pediatr Soc 1989;32:1369–1376.

40. Kim H, Kim K, Kim J, Cho Y, Kim D, Choi T. Genomic diversity of human rotaviruses, a cause of diarrhea in Korean children: 1989-1994. J Korean Soc Microbiol 1997;32:237–244.

41. Shim SY, Jung YC, Le VP, Son DW, Ryoo E, Shim JO, et al. Genetic variation of G4P[6] rotaviruses: evidence for novel strains circulating between the hospital and community. J Med Virol 2010;82:700–706.
crossref pmid
42. Le VP, Chung YC, Kim K, Chung SI, Lim I, Kim W. Genetic variation of prevalent G1P[8] human rotaviruses in South Korea. J Med Virol 2010;82:886–896.
crossref pmid
43. Min BS, Noh YJ, Shin JH, Baek SY, Kim JO, Min KI, et al. Surveillance study (2000 to 2001) of G- and P-type human rotaviruses circulating in South Korea. J Clin Microbiol 2004;42:4297–4299.
crossref pmid pmc
44. Matthijnssens J, Ciarlet M, McDonald SM, Attoui H, Banyai K, Brister JR, et al. Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG). Arch Virol 2011;156:1397–1413.
crossref pmid pmc
45. Santos N, Hoshino Y. Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev Med Virol 2005;15:29–56.
crossref pmid
46. Song MO, Kim KJ, Chung SI, Lim I, Kang SY, An CN, et al. Distribution of human group a rotavirus VP7 and VP4 types circulating in Seoul, Korea between 1998 and 2000. J Med Virol 2003;70:324–328.
crossref pmid
47. Moon SS, Green YS, Song JW, Ahn CN, Kim H, Park KS, et al. Genetic distribution of group A human rotavirus types isolated in Gyunggi province of Korea, 1999-2002. J Clin Virol 2007;38:57–63.
crossref pmid
48. Le VP, Kim JY, Cho SL, Nam SW, Lim I, Lee HJ, et al. Detection of unusual rotavirus genotypes G8P[8] and G12P[6] in South Korea. J Med Virol 2008;80:175–182.
crossref pmid
49. Shim JO, Baek IH, Le VP, Ko EM, Seok WS, Uh Y, et al. Molecular characterization of rotavirus diarrhea among children in South Korea: detection of an unusual G11 strain. Arch Virol 2011;156:887–892.
crossref pmid
50. Lee SY, Hong SK, Lee SG, Suh CI, Park SW, Lee JH, et al. Human rotavirus genotypes in hospitalized children, South Korea, April 2005 to March 2007. Vaccine 2009;27(Suppl 5): F97–F101.
crossref pmid
51. Park S, Oh S, Lee J, Park G, Choi S, Chae Y, et al. Genotypes of rotavirus associated with acute gastroenteritis in Seoul, Korea. Microbiol Immunol 2011;55:641–644.
crossref pmid
52. Huh JW, Kim WH, Yoon MH, Lim YH. Genotypic distribution of rotavirus strains causing severe gastroenteritis in Gyeonggi province, South Korea, from 2003 to 2005. Arch Virol 2009;154:167–170.
crossref pmid
53. Kang JO, Kilgore P, Kim JS, Nyambat B, Kim J, Suh HS, et al. Molecular epidemiological profile of rotavirus in South Korea, July 2002 through June 2003: emergence of G4P[6] and G9P[8] strains. J Infect Dis 2005;192(Suppl 1): S57–S63.
crossref pmid
54. Han TH, Kim CH, Chung JY, Park SH, Hwang ES. Genetic characterization of rotavirus in children in South Korea from 2007 to 2009. Arch Virol 2010;155:1663–1673.
crossref pmid
55. Jin Q, Ward RL, Knowlton DR, Gabbay YB, Linhares AC, Rappaport R, et al. Divergence of VP7 genes of G1 rotaviruses isolated from infants vaccinated with reassortant rhesus rotaviruses. Arch Virol 1996;141:2057–2076.
crossref pmid
56. Kim JS, Kang JO, Cho SC, Jang YT, Min SA, Park TH, et al. Epidemiological profile of rotavirus infection in the Republic of Korea: results from prospective surveillance in the Jeongeub District, 1 July 2002 through 30 June 2004. J Infect Dis 2005;192(Suppl 1): S49–S56.
crossref pmid
57. Than VT, Kang H, Lim I, Kim W. Molecular characterization of serotype G9 rotaviruses circulating in South Korea between 2005 and 2010. J Med Virol 2013;85:171–178.
crossref pmid
58. Clark HF, Hoshino Y, Bell LM, Groff J, Hess G, Bachman P, et al. Rotavirus isolate WI61 representing a presumptive new human serotype. J Clin Microbiol 1987;25:1757–1762.
crossref pmid pmc
59. Kang JO, Kim CR, Kilgore PE, Choi TY. G and P genotyping of human rotavirus isolated in a university hospital in Korea: implications for nosocomial infections. J Korean Med Sci 2006;21:983–988.
crossref pmid pmc
60. Jeong HS, Lee KB, Jeong AY, Jo MY, Jung SY, Ahn JH, et al. Genotypes of the circulating rotavirus strains in the seven prevaccine seasons from September 2000 to August 2007 in South Korea. Clin Microbiol Infect 2011;17:232–235.
crossref pmid
61. Than VT, Baek IH, Kim W. Whole genomic analysis reveals the co-evolutionary phylodynamics of Korean G9P[8] human rotavirus strains. Arch Virol 2013;158:1795–1803.
crossref pmid
62. Pietsch C, Liebert UG. Human infection with G12 rotaviruses, Germany. Emerg Infect Dis 2009;15:1512–1515.
crossref pmid pmc
63. Le VP, Kim JB, Shon DH, Chung IS, Yoon Y, Kim K, et al. Molecular characterization of rare G12P[6] rotavirus isolates closely related to G12 strains from the United States, CAU 195 and CAU 214. Arch Virol 2011;156:511–516.
crossref pmid
64. Than VT, Le VP, Lim I, Kim W. Complete genomic characterization of cell culture adapted human G12P[6] rotaviruses isolated from South Korea. Virus Genes 2011;42:317–322.
crossref pmid
65. Hong SK, Lee SG, Lee SA, Kang JH, Lee JH, Kim JH, et al. Characterization of a G11,P[4] strain of human rotavirus isolated in South Korea. J Clin Microbiol 2007;45:3759–3761.
crossref pmid pmc
66. Kapikian AZ, Hoshino Y, Chanock RM. Rotaviruses. Knipe DM, Howley PM, Griffin DE, Martin MA, editors. Fields virology. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2007;:1787–1825.

67. Taniguchi K, Nishikawa K, Urasawa T, Urasawa S, Midthun K, Kapikian AZ, et al. Complete nucleotide sequence of the gene encoding VP4 of a human rotavirus (strain K8) which has unique VP4 neutralization epitopes. J Virol 1989;63:4101–4106.
crossref pmid pmc
68. Rotavirus vaccines. WHO position paper - January 2013. Wkly Epidemiol Rec 2013;88:49–64.
69. O'Ryan M, Linhares AC. Update on Rotarix: an oral human rotavirus vaccine. Expert Rev Vaccines 2009;8:1627–1641.
crossref pmid
70. Araujo EC, Clemens SA, Oliveira CS, Justino MC, Rubio P, Gabbay YB, et al. Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants. J Pediatr (Rio J) 2007;83:217–224.
crossref pmid
71. Vesikari T, Karvonen A, Prymula R, Schuster V, Tejedor JC, Cohen R, et al. Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study. Lancet 2007;370:1757–1763.
crossref pmid
72. Salem K, Bdour S, Zeller M, Van Ranst M, Matthijnssens J. Genotypes of rotavirus strains circulating in Amman, Jordan, in 2006/07 and their significance for the potential effectiveness of future rotavirus vaccination. Arch Virol 2011;156:1543–1550.
crossref pmid
73. Kang HY, Kim KH, Kim JH, Kim HM, Kim J, Kim MS, et al. Economic evaluation of the national immunization program of rotavirus vaccination for children in Korea. Asia Pac J Public Health 2013;25:145–158.
crossref pmid
74. Kim JS, Bae CW, Lee KY, Park MS, Choi YY, Kim KN, et al. Immunogenicity, reactogenicity and safety of a human rotavirus vaccine (RIX4414) in Korean infants: a randomized, double-blind, placebo-controlled, phase IV study. Hum Vaccin Immunother 2012;8:806–812.
crossref pmid
75. Kim DS, Lee TJ, Kang JH, Kim JH, Lee JH, Ma SH, et al. Immunogenicity and safety of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine in healthy infants in Korea. Pediatr Infect Dis J 2008;27:177–178.
crossref pmid
Fig. 1
Distribution of human group A rotavirus G and P genotypes (n=8,154) determined by analysis of strains collected between 1989 and 2009, and comparison between the distributions of the genotypes before (1989-2007) and after (2007-2009) the introduction of rotavirus vaccines in the population.
Fig. 2
Phylogeny of the currently circulating G and P genotypes in South Korea. The different genotypes are indicated within their respective lineages and sublineages. Numbers at the nodes indicate the level of bootstrap support (%) based on neighbor-joining analysis of 1,000 resampled datasets. Only values above 50% are provided. The accession numbers and nomenclature of the strains used in this study are provided in Supplementary Table 1. (A) Phylogeny of the usual/unusual G genotypes. (B) Phylogeny of the usual/unusual P genotypes.
Table 1
Prevalence of the G and P genotypes of group A rotavirus in South Korea between 1989 and 2009, and comparison between the prevalence of the genotypes before (1989-2007) and after (2007-2009) the introduction of rotavirus vaccines in the population
METRICS Graph View
  • 20 Crossref
  • 24 Scopus
  • 7,556 View
  • 94 Download