OsongPublicHealthResPerspect20123(1),36e42 doi:10.1016/j.phrp.2012.01.006 pISSN2210-9099 eISSN2233-6052 - - ORIGINAL ARTICLE Phylogenetic Analysis of the Rotavirus Genotypes < Originated from Children 5 Years of Age in 16 Cities in South Korea, between 2000 and 2004 Ho-Kyung Oha,b, Seung-Hwa Honga, Byung-Yoon Ahnb, Hye-Kyoung Minc,* aNational Center for Lot Release, National Institute of Food & Drug Safety Evaluation, Korea Food & Drug Administration, Osong, Korea. bSchool of Life Sciences and Biotechnology, Korea University, Seoul, Korea. cDepartment of Biopharmaceuticals & Herbal Medicine Evaluation, Korea Food & Drug Administration, Osong, Korea. Received:December8, Abstract 2011 Objectives:ThepurposeofthisstudywastoexaminethediversityoftheGandP Revised:January15, types ofhuman rotavirusstrainsisolated inSouthKoreaduring 2000 to 2004. 2012 Methods: We selected 38 Group A rotavirus isolates among 652 fecal samples, Accepted: January20, which were collected from infants and children < 5 years of age with acute 2012 gastroenteritis or diarrhea admitted in 8 hospitals representative of five prov- incesofSouthKoreabetween2000and2004.RotavirusP-andG-genotypeswere KEYWORDS: determinedbynucleotidesequencingandphylogeneticanalysiswasperformed. Results: One G1P[4] consisted G1-Id-P[4]-V; one G1P[6] consisted G1-Id-P[6]-Ia; humanrotavirusvaccine, nineG1P[8]consistedG1-Ib-P[8]-Ia(nZ3),G1-Ic-P[8]-Ia(nZ1),andG1-Id-P[8]-Ia phylogeneticanalysis, (nZ5);13G2P[4]consistedG2-V-P[4]-V;twoG3P[4]consistedG3-IIId-P[4]-V;five rotavirus, G3P[8] consisted G3-IIId-P[8]-Ia; four G4P[6] consisted G4-Ie-P[6]-Ia; two G4P[8] SouthKorea, consistedG4-Ie-P[8]-II;oneG9P[6]consistedG9-III-P[6]-Ia. viralgastroenteritis Conclusions:Aconsiderableamountofrotavirusgenotypicdiversitywasdetected in South Korea from 2000 to 2004. These findings are important to develop the effectivevaccinesandtoundertakeepidemiologicstudies. 1. Introduction double-stranded RNA surrounded by a triple-layered capsid consisting of a core, inner capsid, and outer GroupArotavirus,themostcommonetiologicagent capsid. The outer capsid is composed of two structural of severe diarrhea in children, causes about 600,000 proteins, VP4 and VP7, which define virus G(VP4) or deathsperyear[1].Rotavirus,whichisagenusbelonging P(VP7) serotype specificity [2]. Although at least 15 G totheReoviridaefamily,hasagenomeof11segmentsof genotypesand26Pgenotypesareknown[3e8],themost *Correspondingauthor. E-mail:[email protected] 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)whichpermitsunrestrictednon-commercialuse,distribution,andreproductionin anymedium,providedtheoriginalworkisproperlycited. Copyrightª2012KoreaCentersforDiseaseControlandPrevention.PublishedbyElsevierKoreaLLC.Allrightsreserved. Rotavirus in South Korea 37 prevalentP-GcombinationsinhumansareG1P[8],G2P were subjected to seminested multiplex Reverse Tran- [4],G3P[8],G4P[8]andG9P[8].InKorea,rotavirusis scriptase-Polymerase Chain Reaction (RT-PCR) using still the most common viral agent of acute diarrhea in conserved and type specific primers (VP7-G1, G2, G3, youngchildren.AlthoughG1P[8]wasthemostprevalent G4, and G9, and VP4-P[4], P[6], and P[8])[14e18]. strainuntil1997regardlessofgeographicareaorseason The PCR amplicons were purified using a commercial [6,9], the predominant G type strain has shifted to spin column method (QiagenGmbH, Hilden, Germany) othergenotypesincludingG4,G2orG9[10e13].Inthe and sequenced automatically using the ABI PRISM presentstudy,weexaminedthediversityoftheGandP 3100 automated DNA sequencer (Applied Biosystems, typesofhumanrotavirusstrainsisolatedinSouthKorea Inc, Foster city, California, USA). during 2000 e 2004 periods. As a result, we confirmed thattotalnineP-Ggenotypicisolateswereidentified. 2.3. Phylogenetic analysis of nucleotide sequences The VP4 and VP7 sequences obtained were aligned 2. Methods and compared with others VP4 and VP7 sequences of rotaviruses available in the Genebank database (http:// 2.1. Sample collection www.ncbi.nlm.nih.gov/genbank/). Phylogenetic trees of A total of 38 rotavirus isolates were selected among alignment were constructed using the neighbor-joining 652 fecal samples, which were collected from infants method by bootstrapping with 1000 replicates and and children < 5 years of age with acute gastroenteritis phylogeneticdistancesweremeasuredbytheTajima-Nei ordiarrheaadmittedineighthospitalsrepresentativefor model [19] implements in the Molecular Evolutionary five provinces of South Korea between 2000 and 2004. Genetics Analysis (MEGA) (http://www.megasoftware. Humanrotavirusesweredetectedin354of652(54.3%) net/) analytical package (version 5.05, Institute of fecal samples by enzyme-linked immunosorbent assay Molecular Evolutionary Genetics and Department of (ELISA).GandPgenotypesweredetectedbymultiplex Biology,PennsylvaniaStateUniversity,UniversityPark, polymerase chain reaction (PCR) in 316 (89.3%) and Pennsylvania state, USA). 327(92.4%)ofthesesample, respectively.Thelocation oftheseareaswasplottedonthemapofSouthKoreais 2.4. Nucleotide sequence accession numbers shown Figure 1. The VP4 nucleotide sequences of the human rota- virus in this study were assigned accession numbers 2.2. Nucleotide sequencing EF015885,EF077317-EF077322,EF077324-EF077342, Human rotavirus (HRV) double-stranded RNA EF077344, EF077345, and EF0773347-EF077356. The (dsRNA) was extracted using a QIAamp Viral RNA kit VP7 nucleotide sequences were deposited in NCBI Gen- (Qiagen GmbH, Hilden, Germany) in accordance with Bank under accession numbers HQ425255-HQ425292. the manufacturer’s instructions. The dsRNA samples The referenced sequences in the GenBank database are shown in Table 1. 3. Results Most of the fecal samples were collected from Gyunggi province (306/652), followed by Gyeongsang province (130/652), Chungcheong province (88/652), Gangwon province (85/652), Jeolla province (43/652). TheseareshowninFigure1.Among652stoolsamples, 354(54.3%)childrenbelow5yearsofagewerereactive in ELISA. G and P genotypes in parallel were detected by multiplex PCR in 314(88.7%) of these samples. Duringthe2000e2004period,nineP-Gcombinations (NZ314)areprevalentinSouthKorea.Overall,G2P[4] (53.5%) was the most dominant, followed by G1P[8] (16.6%),G1P[6](13.7%),G4P[6](7.3%),G4P[8](5.7%), G3P[8](1.3%), G3P[4](1.0%), G1P[4] (0.6%) and G9P [6](0.3%),whichareshownTable2.G2P[4][Gyunggi (47.0%), Gangwon (58.1%), Chungcheong (46.9%), Jeolla(36.8%),andGyeongsang(70.4%)]wasthedomi- Figure 1. Location of the five provinces used in this study. nant combination of genotypes. However, subdominant Numbers inparentheses indicate thenumberofcase. combinationsweredifferentinfiveprovinces.G1P[6]and 38 H.-K. Oh, et al Table 1. Reference sequence ofthis study Strains VP4 VP7 Strains VP4 VP7 Strains VP4 VP7 MMC71 EU979382 EU839912 AK26 JF304929 JF304931 D205 JF304918 JF304920 mcs/13-07 EU753965 EU753963 Wa M96825 M21843 NIV929893 DQ887060 DQ886957 GER31-08 GU979199 GU979198 GER198-08 GU393007 GU393006 GER173-08 GU392999 GU392998 GER125-08 GU392991 GU392990 GER96-08 GU392987 GU392986 GER84-08 GU392981 GU392980 GER67 GU392979 GU392978 GER15-08 GU392975 GU392974 CMH146/05 GU288635 288626 GER20-08 GU392977 GU392976 CMH032/05 GU288631 GU288623 CMH008/05 GU288627 GU288621 CMH054/05 GU288633 GU288624 GR846/86 AF161829 AF161822 NB123/86 AF161828 AF161821 NB187/86 AF161827 AF161820 GR442/86 AF161824 AF161817 Kagawa/88-349 AB039937 AB039033 Kagawa/88-104 AB039935 AB039030 Kagawa/90-544 AB039939 AB039026 Kagawa/90-554 AB039941 AB039025 Hochi/ AB039943 AB039035 Odelia/ AB039942 AB039034 YO AB008279 D86284 Tokyo-1980 Tokyo-1984 CAU160 EU679396 EU679390 CAU164 EU679398 EU679392 KR/Seoul-661 HM131007 HM130944 KR/Seoul-697 HM131012 HM130949 OM67 HQ127436 AJ491179 F45 U30716 AB180970 AU19 AB017917 AB018697 ST3 EF672612 EF672616 TE56 AF183869 AF183856 Py9856 EU045216 DQ015681 DS-1 AB118025 AB118023 KR/Seoul-638 HM131021 HM130965 MW333 AJ278256 AJ278257 rj5323/02 DQ857926 DQ857953 MMC6 EU839950 EU839923 Py99449 EU045222 DQ015687 BP1227/02 AJ621505 BP271/00 AJ621502 VN846/2003 EF179117 MW670 AJ302146 VN-281 DQ508167 Kor-64 U26378 PA5/90 DQ377573 CH631 AF183857 VN846/2003 EF545000 KR/Seoul-708 HM130955 KR/Seoul-710 HM130956 64SB/96 AY261341 MO D86280 T108 AF450293 CC425 AJ311738 CHW17 D86276 A131 L35055 CMH222 AY707792 Arg928 AF373918 VA75 M86833 MW4086 FJ386453 KUMS00-74 DQ478420 G1P[8] prevailed in Gyunggi province (20.1%, 17.2%), minorlineages(Ia-Ie)inthephylogeneticanalysis.TheG1 G1P[8]prevailedinGangwonprovince(25.8%),G1P[8], rotavirusessegregatedintosevenmajorlineages(IeVII) G4P[6]andG4P[8]prevailedinChungcheongprovince asreported by Arista andcolleagues [20]. Most ofthese (18.4%, 14.3% and 14.3%), and G1P[6] prevailed in isolatesareclusteredinsub-lineageId(nZ7),followed Gyeongsangprovince(13.6%).Also,G1P[8]andG3P[8] by sublineage Ib (nZ3) and sublineage Ic (nZ1). prevailedinJeollaprovince. SublineageIdisolatesshowed97.8%w99.2%nucleotide ToexaminetheVP7andVP4nucleotidesequencesfor sequencesimilaritytostrainGER15-08,andsublineageIb 38 isolates among 314 identified isolates, phylogenetic isolatesshowed99.3%w99.6%nucleotidesimilaritywith trees for G type (G1, G2, G3, G4, and G9) and P type strainsVN-281.KMR267isolatesinsublineageIcshowed [P(4), P(6), P(8)) were constructed by applying the 99.5%nucleotidesimilaritytoPy9856.AmongelevenG1 neighbor-joining method. Sequences of VP7 and VP4 rotavirus isolates, the three G1-Ib isolate was associated were determined from 38 representative rotaviruses, withP[8]-IIIa.OneG1-IcwasassociatedwithP[8]-IIIa comprising the different genotypes and intra genotypic andsevenG1-IdisolateswereassociatedwithP[4]-V,P lineagesdetectedbypartialsequencing.Sequencesofthe [6]-Ia,andP[8]-IIIa. representativeisolatesweresubmittedtoGenBank(Table TheG2rotavirusessegregatedintofivemajorlineages 3)andincludedinthephylogeneticanalysis(Figures2and (IeV) [21]. The thirteen G2 rotavirus isolates clustered 3).Inthisstudy,the11G1rotavirusisolatesshowedthat under lineage V. They showed 99.2w99.5% nucleotide theyareapartofthelineageIandareclusteredintofive similarity to strain GER84-08 from Germany. All G2-V Table 2. Distribution of group A rotavirus P-G combination strains among infants and children below 5 years of age with diarrhea in five provincesof South Koreabetween 2000and2004 Number ofP-G combinationstrains (%) Provinces G1P[4] G1P[6] G1P[8] G2P[4] G3P[4] G3P[8] G4P[6] G4P[8] G9P[6] Total Gyunggi 2(1.5) 27(20.1) 23(17.2) 63(47.0) 3(2.2) 0(0.0) 11(8.2) 5(3.7) 0(0.0) 134(42.7) Gangwon 0(0.0) 1(3.2) 8(25.8) 18(58.1) 0(0.0) 0(0.0) 1(3.2) 2(6.5) 1(3.2) 31(9.9) Chungcheong 0(0.0) 3(6.1) 9(18.4) 23(46.9) 0(0.0) 0(0.0) 7(14.3) 7(14.3) 0(0.0) 49(15.6) Jeolla 0(0.0) 1(5.3) 6(31.6) 7(36.8) 0(0.0) 4(21.1) 1(5.3) 0(0.0) 0(0.0) 19(6.1) Gyeongsang 0(0.0) 11(13.6) 6(7.4) 57(70.4) 0(0.0) 0(0.0) 3(3.7) 4(4.9) 0(0.0) 81(25.8) Total 2(0.6) 43(13.7) 52(16.6) 168(53.5) 3(1.0) 4(1.3) 23(7.3) 18(5.7) 1(0.3) 314 Rotavirus in South Korea 39 Table3. TheGandPgenotypesofthe38representativerotavirusstrainsofthisstudyaregiven.TheVP7andVP4sequences weresubmittedtoGenBankandtheaccordantaccessionnumbersareprovidedinbrackets.Patientage,gender,city of samplecollection, and theyearofsample collectionare indicated Patientage Cityof Yearof Isolates Ggenotype(Acc.no.) Pgenotypes(Acc.no.) (month) Patientsex collection collection KMR004 G1-Id(HQ425255) P[8]-IIIa(EF077330) 11 M Seoul 2002 KMR010 G3-IIId(HQ424279) P[4]-V (EF077353) 11 F Seoul 2003 KMR012 G3-IIId(HQ425280) P[8]-IIIa(EF077336) 11 M Seoul 2003 KMR021 G2-V(HQ422566) P[4]-V (EF077344) 47 F Seoul 2002 KMR023 G1-Id(HQ425256) P[8]-IIIa(EF077350) 47 M Seoul 2002 KMR024 G2-V(HQ425267) P[4]-V (EF077345) 8 M Seoul 2002 KMR028 G4-Ie(HQ425287) P[6]-Ia (EF077334) 47 F Seoul 2003 KMR025 G4-Ie(HQ425286) P[6]-Ia (EF077348) 11 F Seoul 2002 KMR029 G2-V(HQ425268) P[4]-V (EF077354) 2 F Seoul 2003 KMR037 G2-V(HQ425269) P[4]-V (EF015885) 4 M Seoul 2000 KMR044 G1-Id(HQ425257) P[4]-V (EF077332) 6 M Seoul 2003 KMR053 G4-Ie(HQ425288) P[6]-Ia (EF077341) 23 F Incheon 2004 KMR057 G2-V(HQ425270) P[4]-V (EF077317) 31 F Incheon 2000 KMR058 G1-Ib(HQ425258) P[8]-IIIa(EF077342) 1 F Incheon 2004 KMR060 G3-IIId(HQ425281) P[4]-V (EF077347) 11 F Incheon 2004 KMR101 G1-Id(HQ425259) P[8]-IIIa(EF077338) 23 M Seoul 2003 KMR106 G2-V(HQ425271) P[4]-V (EF077356) 4 M Seoul 2000 KMR126 G2-V(HQ425272) P[4]-V (EF077340) 48 M Seoul 2004 KMR184 G2-V(HQ425273) P[4]-V (EF077318) 23 M Daegu 2000 KMR267 G1-Ic(HQ425260) P[8]-IIIa(EF077319) 23 F Daejeon 2000 KMR294 G1-Id(HQ425261) P[6]-Ia (EF077352) 1 M Masan 2000 KMR419 G1-Id(HQ425262) P[8]-IIIa(EF077320) 4 M Gwangju 2000 KMR538 G4-Ie(HQ425289) P[8]-II (EF077331) 36 M Gangneung 2000 KMR541 G4-Ie(HQ425290) P[8]-II (EF077333) 24 M Gangneung 2000 KMR547 G2-V(HQ425274) P[4]-V (EF077349) 48 F Gangneung 2000 KMR548 G2-V(HQ425275) P[4]-V (EF077351) 36 F Gangneung 2000 KMR580 G1-Ib(HQ425263) P[8]-IIIa(EF077335) 40 M Gangneung 2000 KMR720 G9-III(HQ425292) P[6]-Ia (EF077329) 1 F Gangneung 2000 KMR733 G1-Ib(HQ425264) P[8]-IIIa(EF077339) 19 M Gangneung 2001 KMR748 G1-Id(HQ425265) P[8]-IIIa(EF077325) 18 F Gwangju 2001 KMR750 G2-V(HQ425276) P[4]-V (EF077321) 3 F Busan 2001 KMR751 G3-IIId(HQ425282) P[8]-IIIa(EF077326) 19 M Gwangju 2001 KMR757 G2-V(HQ425277) P[4]-V (EF077337) 5 M Masan 2001 KMR766 G3-IIId(HQ425283) P[8]-IIIa(EF077327) 1 M Gwangju 2001 KMR769 G2-V(HQ425278) P[4]-V (EF077322) 3 M Masan 2001 KMR773 G3-IIId(HQ425284) P[8]-IIIa(EF077328) 6 M Gwangju 2001 KMR787 G3-IIId(HQ425285) P[8]-IIIa(EF077355) 3 M Gwangju 2001 KMR792 G4-Ie(HQ425291) P[6]-Ia (EF077324) 7 F Daejeon 2001 Acc.no.ZGenBankAccessionNumber. isolates were associated with P[4]-V. Meanwhile, the isolate exhibited 98.4%w98.7% nucleotide sequence seven G3 strains are a part of the sublineage IIId and similarity to TE56, G9 isolate, KMR720 exhibited showed 99.3%w99.5% sequence similarity to strain 97.1% nucleotide sequence similarity to GR846/86. GER198-08.ThetwoG3-IIIdwereassociatedwithP[4]- While P[8]-IIIa exhibited 97.6%w 99.4% nucleotide V, and five G3-IIId were associated with P[8]-IIIa. The similaritytostrainsCMH032/05,P[8]-IIexhibited99.4% 16 P[4]-V including G1-Id, G2-V, and G3-IIId shared nucleotidesequence similarity to strain Kagawa/88-104. more than 97.6% nucleotide similarity, and the six G4 As a result, we confirm that a total of nine P-G geno- rotavirus strains clustered in sub-lineage Ie compared to typicisolateswereidentified(11P-Gsubgenotypes). strains KUMS00-74 has 98.7-99.4% nucleotide simi- larity. The four G4-Ie were associated with P[6]-Ia and twoG4-IewereassociatedwithP[8]-II.Finally,theone 4. Discussion G9isolate,KMR720showedhighsequencesimilarityto all lineage III strains (more than 98.3%) and associated Rotaviruses have been described as a major cause of with P[6]-Ia. While the five P[6]-Ia excluding G9 severe diarrhea among infants and young children in 40 H.-K. Oh, et al Figure2. PhylogeneticanalysisofVP7genenucleotidesequencesofGroupArotavirusstrainsfromKoreabetween2000and 2004.Phylogenetictreesofalignmentwereconstructedusingtheneighbor-joiningmethodbybootstrappingwith1000replicates, and phylogenetic distances were measured by Tajima-Nei model. Only values > 50% are given. Numbers at nodes indicate the levelof bootstrapsupport(%). Barrepresents 0.05substitutionsper nucleotideposition. Rotavirus in South Korea 41 Figure3. PhylogeneticanalysisofVP4genenucleotidesequencesofGroupArotavirusstrainsfromKoreabetween2000and 2004.Phylogenetictreesofalignmentwereconstructedusingtheneighbor-joiningmethodbybootstrappingwith1000replicates, and phylogenetic distances were measured by Tajima-Nei model. Only values > 50% are given. Numbers at nodes indicate the levelof bootstrapsupport(%). Barrepresents 0.05substitutionsper nucleotideposition. 42 H.-K. Oh, et al South Korea. Epidemiologic studies worldwide have 2. ZhouYJ,BurnsJW,MoritaY,etal.LocalizationofrotavirusVP4 revealed that five P-G combinations, G1P[8], G2P[4], neutralization epitopes involved in antibody-induced conforma- G3P[8],G4P[8],andG9P[8],havebeenlinkedtomost tionalchangesofvirusstructure.JVirol1994Jun;68(6):3955e64. 3. RahmanM,BanikS,FaruqueASG,etal.Detectionandcharac- of the cases of rotavirus diarrhea among infants and terization of human group C rotaviruses in Bangladesh. J Clin young children worldwide. In this study, we confirmed Microbiol2005Sep;43(9):4460e5. both uncommon P-G combinations [G1P(4), G1P(6), 4. Santos N, Hoshino Y. Global distribution of rotavirus seroty- G3P(4), G4P(6), and G9P(6)] as well as most common pes/genotypes and its implication for the development and P-G combinations [G1P(8), G2P(4), G3P(8), and implementationofaneffectiverotavirusvaccine.RevMedVirol 2005Jan;15(1):29e56. G4P(8))] There are two oral live vaccines available in 5. Samajdar S, Varghese V, Barman P, et al. Changing pattern of Korea; Rotarix (GlaxoSmithKline, Rixensart, Belgium) human group A rotaviruses: emergence of G12 as an important is a monovalent vaccine that consists of the attenuated pathogenamongchildrenineasternIndia.JClinVirol2006Jul; G1P[8]humanrotavirusstrainRIX4414andhasbeenin 36(3):183e8. 6. MoonSS,SongGreenYS,SongJW,etal.Geneticdistributionof useinKoreasince2008.Rotateq(MERCK&CO.,INC, group A human rotavirus types isolated in Gyunggi province of Pennsylvania, USA) is a pentavalent vaccine which Korea,1999-2002.JClinVirol2007Jan;38(1):57e63. consists of five attenuated human-bovine reassortant 7. VarshneyB,JagannathMR,VethanayagamRR,etal.Prevalence viruses [G1 to G4 and P(8)]; G1: human W179-bovine of, and antigenic variation in, serotype G10 rotaviruses and WC3 reassortant, G2: human SC2-bovine WC3 reas- detectionofserotypeG3strainsindiarrheiccalves:implicationsfor sortant,G3:W178-bovine WC3reassortant, G4:human theoriginofG10P11orP11typereassortantasymptomaticstrains innewbornchildreninIndia.ArchVirol2002Jan;147(1):143e65. BrB-bovine WC3 reassortant, P1A[8]: human W179- 8. Martella V, Banyai K, Ciarlet M, et al. Relationships among bovine WC3 reassortant. It hasbeen available inKorea porcine and human P[6] rotaviruses: evidence that the different since2007.Althoughthesevaccinesareeffectiveonmost human P[6] lineages have originated from multiple interspecies common P-G combinations, G2P[4], G1P[8], G3P[8], transmissionevents.Virology2006Jan;344(2):509e19. G4P[8],andG9P[8],thosemayfailtoworkontheother 9. LeVP,ChungYC,KimKJ,etal.Geneticvariationofprevalent G1P[8]humanrotavirusesinSouthKorea.JMedVirol2010May; genotypes. Allthings considered, developmentof multi- 82(5):886e96. valent rotavirus vaccine including new ones must be 10. MinBS,NohYJ,ShinJH,etal.Surveillancestudy(2000to2001) required. Therefore, this study will provide useful infor- ofG-andP-typehumanrotavirusescirculatinginSouthKorea.J mationforthedevelopmentofeffectiverotavirusvaccines ClinMicrobiol2004Sep;42(9):4297e310. 11. Kang JO, Kilgore P, Kim JS, et al. Molecular epidemiological inthefuture.Also,theinternationalrelationshiphasbeen profileofrotavirusinSouthKorea,July2002throughJune2003: limitedbythegeographiclocationinthepast,butnowit emergenceofG4P[6]andG9P[8]strains.JInfectDis2005Sep; has expanded all over the world, and this expansion is 192(Suppl.1):S57e63. thoughttobethecauseofthechangeinstrains. 12. Kim JS, Kang JO, Cho SC, 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 Sep;192(Suppl. 1): 5. Conclusion S49e56. 13. SongMO,KimKJ,ChungSI,etal.Distributionofhumangroup Consequently, the P-G combination genotypes of a rotavirus VP7 and VP4 types circulating in Seoul, Korea this study would serve as useful information for the between1998and2000.JMedVirol2003Jun;70(2):324e8. development of effective rotavirus vaccines. Such P-G 14. Das BK, Gentsch JR, Cicirello HG, et al. 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