Abstract
The exact evolutionary patterns of human G4P[6] rotavirus strains remain to be elucidated. Such strains possess unique and strain-specific genotype constellations, raising the question of whether G4P[6] strains are primarily transmitted via independent interspecies transmission or human-to-human transmission after interspecies transmission. Two G4P[6] rotavirus strains were identified in fecal specimens from hospitalized patients with severe diarrhea in Thailand, namely, DU2014-259 (RVA/Human-wt/THA/DU2014-259/2014/G4P[6]) and PK2015-1-0001 (RVA/Human-wt/THA/PK2015-1-0001/2015/G4P[6]). Here, we analyzed the full genomes of the two human G4P[6] strains, which provided the opportunity to study and confirm their evolutionary origin. On whole genome analysis, both strains exhibited a unique Wa-like genotype constellation of G4-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1. The NSP1 genotype A8 is commonly found in porcine rotavirus strains. Furthermore, on phylogenetic analysis, each of the 11 genes of strains DU2014-259 and PK2015-1-0001 appeared to be of porcine origin. On the other hand, the two study strains consistently formed distinct clusters for nine of the 11 gene segments (VP4, VP6, VP1-VP3, and NSP2-NSP5), strongly indicating the occurrence of independent porcine-to-human interspecies transmission events. Our observations provide important insights into the origin of zoonotic G4P[6] strains, and into the dynamic interaction between porcine and human rotavirus strains.











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The nucleotide sequence data obtained in this study have been deposited in the DDBJ and EMBL/GenBank data libraries. The accession numbers for the nucleotide sequences of the VP1-VP4, VP6, VP7, and NSP1-NSP5 gene segments of strains DU2014-259 and PK2015-1-0001 are LC569880-LC569890 and LC569891-LC569901, respectively.
References
Tate JE, Burton AH, Boschi-Pinto C, Parashar UD; World Health Organization-Coordinated Global Rotavirus Surveillance Network (2016) Global, regional, and national estimates of rotavirus mortality in children <5 years of age, 2000–2013. Clin Infect Dis 62(Suppl. 2):S96–S105
Troeger C, Khalil IA, Rao PC, Cao S, Blacker BF, Ahmed T, Armah G, Bines JE, Brewer TG, Colombara DV, Kang G, Kirkpatrick BD, Kirkwood CD, Mwenda JM, Parashar UD, Petri WA Jr, Riddle MS, Steele AD, Thompson RL, Walson JL, Sanders JW, Mokdad AH, Murray CJL, Hay SI, Reiner RC Jr (2018) Rotavirus vaccination and the global burden of rotavirus diarrhea among children younger than 5 years. JAMA Pediatr 172:958–965
Estes MK, Greenberg HB (2013) Rotaviruses. In: Knipe PM, Howley DM (eds) Fields Virology, 6th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1347–1401
Ghosh S, Kobayashi N (2011) Whole-genomic analysis of rotavirus strains: current status and future prospects. Future Microbiol 6:1049–1065
Papp H, Borzák R, Farkas S, Kisfali P, Lengyel G, Molnár P, Melegh B, Matthijnssens J, Jakab F, Martella V, Bányai K (2013) Zoonotic transmission of reassortant porcine G4P[6] rotaviruses in Hungarian pediatric patients identified sporadically over a 15 year period. Infect Genet Evol 19:71–80
Martella V, Bányai K, Matthijnssens J, Buonavoglia C, Ciarlet M (2010) Zoonotic aspects of rotaviruses. Vet Microbiol 140:246–255
Matthijnssens J, Ciarlet M, Heiman E, Arijs I, Delbeke T, McDonald SM, Palombo EA, Iturriza-Gómara M, Maes P, Patton JT, Rahman M, Van Ranst M (2008) Full genome-based classification of rotaviruses reveals a common origin between human Wa-Like and porcine rotavirus strains and human DS-1-Like and bovine rotavirus strains. J Virol 82:3204–3219
Heiman EM, McDonald SM, Barro M, Taraporewala ZF, Bar-Magen T, Patton JT (2008) Group A human rotavirus genomics: evidence that gene constellations are influenced by viral protein interactions. J Virol 82:11106–11116
Tacharoenmuang R, Komoto S, Guntapong R, Ide T, Haga K, Katayama K, Kato T, Ouchi Y, Kurahashi H, Tsuji T, Sangkitporn S, Taniguchi K (2015) Whole genomic analysis of an unusual human G6P[14] rotavirus strain isolated from a child with diarrhea in Thailand: evidence for bovine-to-human interspecies transmission and reassortment events. PLoS ONE 10:e0139381
Santos N, Hoshino Y (2005) Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev Med Virol 15:29–56
Alkali BR, Daneji AI, Magaji AA, Bilbis LS, Bande F (2016) Molecular characterization of human rotavirus from children with diarrhoeal disease in Sokoto State. Nigeria Mol Biol Int 2016:1876065
Bwogi J, Jere KC, Karamagi C, Byarugaba DK, Namuwulya P, Baliraine FN, Desselberger U, Iturriza-Gomara M (2017) Whole genome analysis of selected human and animal rotaviruses identified in Uganda from 2012 to 2014 reveals complex genome reassortment events between human, bovine, caprine and porcine strains. PLoS ONE 12:e0178855
Degiuseppe JI, Beltramino JC, Millán A, Stupka JA, Parra GI (2013) Complete genome analyses of G4P[6] rotavirus detected in Argentinean children with diarrhoea provides evidence of interspecies transmission from swine. Clin Microbiol Infect 19:E367–E371
Dong HJ, Qian Y, Huang T, Zhu RN, Zhao LQ, Zhang Y, Li RC, Li YP (2013) Identification of circulating porcine-human reassortant G4P[6] rotavirus from children with acute diarrhea in China by whole genome analyses. Infect Genet Evol 20:155–162
Heylen E, Batoko Likele B, Zeller M, Stevens S, De Coster S, Conceição-Neto N, Van Geet C, Jacobs J, Ngbonda D, Van Ranst M, Matthijnssens J (2014) Rotavirus surveillance in Kisangani, the Democratic Republic of the Congo, reveals a high number of unusual genotypes and gene segments of animal origin in non-vaccinated symptomatic children. PLoS ONE 9:e100953
Hwang KP, Wu FT, Bányai K, Wu HS, Yang DC, Huang YC, Lin JS, Hsiung CA, Huang JC, Jiang B, Gentsch JR (2012) Identification of porcine rotavirus-like genotype P[6] strains in Taiwanese children. J Med Microbiol 61:990–997
Ianiro G, Micolano R, Conte M, Labianca M, Vaccari G, Monini M (2019) Detection of an animal-derived G4P[6] group A rotavirus strain in a symptomatic child, in Italy. Virus Res 260:7–11
Imagawa T, Saito M, Yamamoto D, Saito-Obata M, Masago Y, Ablola AC, Tandoc AO 3rd, Segubre-Mercado E, Lupisan SP, Oshitani H (2020) Genetic diversity of species A rotaviruses detected in clinical and environmental samples, including porcine-like rotaviruses from hospitalized children in the Philippines. Infect Genet Evol 85:104465
Kaneko M, Do LP, Doan YH, Nakagomi T, Gauchan P, Agbemabiese CA, Dang AD, Nakagomi O (2018) Porcine-like G3P[6] and G4P[6] rotavirus A strains detected from children with diarrhoea in Vietnam. Arch Virol 163:2261–2263
Kang JO, Kilgore P, Kim JS, Nyambat B, Kim J, Suh HS, Yoon Y, Jang S, Chang C, Choi S, Kim MN, Gentsch J, Bresee J, Glass R (2005) Molecular epidemiological profile of rotavirus in South Korea, July 2002 through June 2003: emergence of G4P[6] and G9P[8] strains. J Infect Dis 192(Suppl 1):S57–S63
Kang Y, Cai Y (2018) Epidemiology and Genetic Diversity of Rotavirus in Kunming, China, in 2015. Intervirology 61:9–13
Kazi AM, Warraich GJ, Qureshi S, Qureshi H, Khan MM, Zaidi AK; members of the Pakistan Rotavirus Study Group (2014) Sentinel hospital-based surveillance for assessment of burden of rotavirus gastroenteritis in children in Pakistan. PLoS ONE 9:e108221
Lee SK, Choi S, Kim JS, Lee EJ, Hyun J, Kim HS (2019) Whole-genome analysis of rotavirus G4P[6] strains isolated from Korean neonates: association of Korean neonates and rotavirus P[6] genotypes. Gut Pathog 11:37
Maestri RP, Kaiano JH, Neri DL, Soares L, Guerra S, Oliveira D, Farias YN, Gabbay YB, Leite JP, Linhares A, Mascarenhas JD (2012) Phylogenetic analysis of probable non-human genes of group A rotaviruses isolated from children with acute gastroenteritis in Belém, Brazil. J Med Virol 84:1993–2002
Malasao R, Khamrin P, Kumthip K, Ushijima H, Maneekarn N (2018) Complete genome sequence analysis of rare G4P[6] rotavirus strains from human and pig reveals the evidence for interspecies transmission. Infect Genet Evol 65:357–368
Martella V, Bányai K, Ciarlet M, Iturriza-Gómara M, Lorusso E, De Grazia S, Arista S, Decaro N, Elia G, Cavalli A, Corrente M, Lavazza A, Baselga R, Buonavoglia C (2006) Relationships among porcine and human P[6] rotaviruses: evidence that the different human P[6] lineages have originated from multiple interspecies transmission events. Virology 344:509–519
Martinez M, Galeano ME, Akopov A, Palacios R, Russomando G, Kirkness EF, Parra GI (2014) Whole-genome analyses reveals the animal origin of a rotavirus G4P[6] detected in a child with severe diarrhea. Infect Genet Evol 27:156–162
Mukherjee A, Ghosh S, Bagchi P, Dutta D, Chattopadhyay S, Kobayashi N, Chawla-Sarkar M (2011) Full genomic analyses of human rotavirus G4P[4], G4P[6], G9P[19] and G10P[6] strains from North-eastern India: evidence for interspecies transmission and complex reassortment events. Clin Microbiol Infect 17:1343–1346
Mun SK, Cho HG, Lee HK, Park SH, Park PH, Yoon MH, Jeong HS, Lim YH (2016) High incidence of group A rotaviruses G4P[6] strains among children in Gyeonggi province of South Korea, from 2009 to 2012. Infect Genet Dis 44:351–355
Nguyen TA, Khamrin P, Trinh QD, Phan TG, Pham l, Hoang l, Hoang KT, Yagyu F, Okitsu S, Ushijima H, (2007) Sequence analysis of Vietnamese P[6] rotavirus strains suggests evidence of interspecies transmission. J Med Virol 79:1959–1965
Pager CT, Alexander JJ, Steele AD (2000) South African G4P[6] asymptomatic and symptomatic neonatal rotavirus strains differ in their NSP4, VP8*, and VP7 genes. J Med Virol 62:208–216
Papp H, László B, Jakab F, Ganesh B, De Grazia S, Matthijnssens J, Ciarlet M, Martella V, Bányai K (2013) Review of group A rotavirus strains reported in swine and cattle. Vet Microbiol 165:190–199
Phan MVT, Anh PH, Cuong NV, Munnink BBO, van der Hoek L, My PT, Tri TN, Bryant JE, Baker S, Thwaites G, Woolhouse M, Kellam P, Rabaa MA, Cotten M; VIZIONS Consortium (2016) Unbiased whole-genome deep sequencing of human and porcine stool samples reveals circulation of multiple groups of rotaviruses and a putative zoonotic infection. Virus Evol 2:vew027
Ramachandran M, Das BK, Vij A, Kumar R, Bhambal SS, Kesari N, Rawat H, Bahl L, Thakur S, Woods PA, Glass RI, Bhan MK, Gentsch JR (1996) Unusual diversity of human rotavirus G and P genotypes in India. J Clin Microbiol 34:436–439
Stupka JA, Carvalho P, Amarilla AA, Massana M, Parra GI, Network ANS, for Diarrheas, (2009) National Rotavirus Surveillance in Argentina: high incidence of G9P[8] strains and detection of G4P[6] strains with porcine characteristics. Infect Genet Evol 9:1225–1231
Wang YH, Kobayashi N, Nagashima S, Zhou X, Ghosh S, Peng JS, Hu Q, Zhou DJ, Yang ZQ (2010) Full genomic analysis of a porcine-bovine reassortant G4P[6] rotavirus strain R479 isolated from an infant in China. J Med Virol 82:1094–1102
Yahiro T, Takaki M, Chandrasena T, Rajindrajith S, Iha H, Ahmed K (2018) Human-porcine reassortant rotavirus generated by multiple reassortment events in a Sri Lankan child with diarrhea. Infect Genet Evol 65:170–186
Zhou X, Wang YH, Ghosh S, Tang WF, Pang BB, Liu MQ, Peng JS, Zhou DJ, Kobayashi N (2015) Genomic characterization of G3P[6], G4P[6] and G4P[8] human rotaviruses from Wuhan, China: evidence for interspecies transmission and reassortment events. Infect Genet Evol 33:55–71
Tacharoenmuang R, Komoto S, Guntapong R, Upachai S, Singchai P, Ide T, Fukuda S, Ruchusatsawast K, Sriwantana B, Tatsumi M, Motomura K, Takeda N, Murata T, Sangkitporn S, Taniguchi K, Yoshikawa T (2020) High prevalence of equine-like G3P[8] rotavirus in children and adults with acute gastroenteritis in Thailand. J Med Virol 92:174–186
Dennis FE, Fujii Y, Haga K, Demanka S, Lartey B, Agbemabiese CA, Ohta N, Armah GE, Katayama K (2014) Identification of novel Ghanaian G8P[6] human-bovine reassortant rotavirus strain by next generation sequencing. PLoS ONE 9:e100699
Komoto S, Adah MI, Ide T, Yoshikawa T, Taniguchi K (2016) Whole genomic analysis of human and bovine G8P[1] rotavirus strains isolated in Nigeria provides evidence for direct bovine-to-human interspecies transmission. Infect Genet Evol 43:424–433
Maes P, Matthijnssens J, Rahman M, Van Ranst M (2009) RataC: a web-based tool for the complete genome classification of group A rotaviruses. BMC Microbiol 9:238
Matthijnssens J, Ciarlet M, McDonald SM, Attoui H, Bányai K, Brister JR, Buesa J, Esona MD, Estes MK, Gentsch JR, Iturriza-Gómara M, Johne R, Kirkwood CD, Martella V, Mertens PP, Nakagomi O, Parreño V, Rahman M, Ruggeri FM, Saif LJ, Santos N, Steyer A, Taniguchi K, Patton JT, Desselberger U, Van Ranst M (2011) Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG). Arch Virol 156:1397–1413
Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680
Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874
Tuanthap S, Vongpunsawad S, Luengyosluechakul S, Sakkaew P, Theamboonlers A, Amonsin A, Poovorawan Y (2019) Genome constellations of 24 porcine rotavirus group A strains circulating on commercial Thai swine farms between 2011 and 2016. PLoS ONE 14:e0211002
Komoto S, Tacharoenmuang R, Guntapong R, Ide T, Tsuji T, Yoshikawa T, Tharmaphornpilas P, Sangkitporn S, Taniguchi K (2016) Reassortment of human and animal rotavirus gene segments in emerging DS-1-like G1P[8] rotavirus strains. PLoS ONE 11:e0148416
Komoto S, Maeno Y, Tomita M, Matsuoka T, Ohfu M, Yodoshi T, Akeda H, Taniguchi K (2013) Whole genomic analysis of a porcine-like human G5P[6] rotavirus strain isolated from a child with diarrhoea and encephalopathy in Japan. J Gen Virol 94:1568–1575
Do LP, Kaneko M, Nakagomi T, Gauchan P, Agbemabiese CA, Dang AD, Nakagomi O (2017) Molecular epidemiology of rotavirus A, causing acute gastroenteritis hospitalizations among children in Nha Trang, Vietnam, 2007–2008: identification of rare G9P[19] and G10P[14] strains. J Med Virol 89:621–631
My PVT, Rabaa MA, Donato C, Cowley D, Phat VV, Dung TTN, Anh PH, Vinh H, Bryant JE, Kellam P, Thwaites G, Woolhouse MEJ, Kirkwood CD, Baker S (2014) Novel porcine-like human G26P[19] rotavirus identified in hospitalized paediatric diarrhoea patients in Ho Chi Minh City. Vietnam J Gen Virol 95:2727–2733
Komoto S, Tacharoenmuang R, Guntapong R, Ide T, Sinchai P, Upachai S, Fukuda S, Yoshikawa T, Tharmaphornpilas P, Sangkitporn S, Taniguchi K (2017) Identification and characterization of a human G9P[23] rotavirus strain from a child with diarrhoea in Thailand: evidence for porcine-to-human interspecies transmission. J Gen Virol 98:532–538
Jere KC, Chaguza C, Bar-Zeev N, Lowe J, Peno C, Kumwenda B, Nakagomi O, Tate JE, Parashar UD, Heyderman RS, French N, Cunliffe NA, Iturriza-Gomara M (2018) Emergence of double- and triple-gene reassortant G1P[8] rotaviruses possessing a DS-1-like backbone after rotavirus vaccine introduction in Malawi. J Virol 92:e01246-e1317
Ghosh S, Urushibara N, Taniguchi K, Kobayashi N (2012) Whole genomic analysis reveals the porcine origin of human G9P[19] rotavirus strains Mc323 and Mc345. Infect Genet Evol 12:471–477
Yodmeeklin A, Khamrin P, Chuchaona W, Kumthip K, Kongkaew A, Vachirachewin R, Okitsu S, Ushijima H, Maneekarn N (2017) Analysis of complete genome sequences of G9P[19] rotavirus strains from human and piglet with diarrhea provides evidence for whole-genome interspecies transmission of nonreassorted porcine rotavirus. Infect Genet Evol 47:99–108
Tuanthap S, Phupolphan C, Luengyosluechakul S, Duang-In A, Theamboonlers A, Wattanaphansak S, Vongpunsawad S, Amonsin A, Poovorawan Y (2018) Porcine rotavirus C in pigs with gastroenteritis on Thai swine farms, 2011–2016. Peer J. 6:e4724
Acknowledgements
We wish to thank the public health staff of Phen and Phrapokklao Hospitals for their great help in collecting specimens and clinical data on the subjects. This study was supported in part by AMED (19fk0108099s0301 and 20fk0108099s0302) (SK), the Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections, RCC-ERI (NT), and the laboratory-based surveillance program for unidentified and possibly new pathogens affecting public health problems in Thailand, IEIP-EID (BS).
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RT, RG, KT, and SK designed the study. Material preparation, data collection, and analyses were performed by RT, SU, PS, TI, SF, RH, KS, SK, NO, TL, KR, YK, BS, KM, MT, NT, TY, TM, and BU. RT, RG, KT, and SK prepared the manuscript.
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This study was approved by the Ethical Review Committee for Research on Human Subjects, Ministry of Public Health, Thailand (Ref. Nos. 10/2555 and 0032/2556).
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Tacharoenmuang, R., Guntapong, R., Upachai, S. et al. Full genome-based characterization of G4P[6] rotavirus strains from diarrheic patients in Thailand: Evidence for independent porcine-to-human interspecies transmission events. Virus Genes 57, 338–357 (2021). https://doi.org/10.1007/s11262-021-01851-y
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DOI: https://doi.org/10.1007/s11262-021-01851-y