2018 ; Vol.28-12: 2133~2140
|Author||Byung-Joo Park, Soon-Tag Jung, Chang-Sun Choi, JinJong Myoung, Hee-Seop Ahn, Sang-Hoon Han, Yong-Hyun Kim, Hyeon-Jeong Go, Joong-Bok Lee, Seung-Yong Park, Chang-Seon Song, Sang-Won Lee, In-Soo Choi|
|Place of duty||Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University,Seoul Korea|
|Title||Pathogenesis of human norovirus genogroup II genotype 4 in post-weaning gnotobiotic pigs|
J. Microbiol. Biotechnol.2018 ;
|Abstract||Norovirus is the most common cause of acute gastroenteritis. Its pathogenesis is poorly understood owing to the difficulty of establishing viral infection in animal models. Here, post-weaning gnotobiotic pigs were infected with human norovirus genogroup II genotype 4 (HuNoV GII.4) to investigate the pathogenesis and replication of the virus. Three groups of four pigs were infected with 1×105, 1×106, or 1×107 genomic equivalent (GE) copies of HuNoV GII.4. Four pigs were used as negative controls. Blood and rectal swab samples were collected after viral infection, and gross legions were examined after necropsy. Diarrhea was induced in 25% and 75% of pigs infected with 1×106 and 1×107 GE copies, respectively. Viral shedding was detected in 50%, 75%, and 50% of pigs infected with 1×105, 1×106, and 1×107 GE copies, respectively. Viremia was detected in 25% of pigs infected with either 1×106 or 1×107 GE copies. When gross lesions of gastroenteritis were investigated, the ileum walls of the infected pigs were thinner than those of the controls. Villi atrophy and inflammatory cell infiltration were identified in the ileum of each infected pig. Viral capsid was identified in the jejunum, ileum, colon, spleen, and mesenteric lymph node. Virus replication was newly verified in the spleen and mesenteric lymph nodes by detection of negative-sense viral RNA. In conclusion, HuNoV GII.4 could induce acute gastroenteritis and replicate in the extra-intestinal lymphoid tissues in post-weaning gnotobiotic pigs. Therefore, such pigs would be a suitable animal model for studying the pathogenesis and replication of HuNoV.|
|Key_word||Norovirus, genotype II, gnotobiotic pig, gastroenteritis, pathogenesis, replication|
Hall AJ, Lopman BA, Payne DC, Patel MM, Gastañaduy PA, Vinjé J, et al. 2013. Norovirus disease in the United States. Emerg. Infect. Dis. 19: 1198-1205.
Maunula L, Roivainen M, Keränen M, Mäkelä S, Söderberg K, Summa M, et al. 2009. Detection of human norovirus from frozen raspberries in a cluster of gastroenteritis outbreaks. Euro. Surveill. 14: 16-18.
Atmar RL, Estes MK. 2006. The epidemiologic and clinical importance of norovirus infection. Gastroenterol Clin. North. Am. 35: 275-290.
Chen SY, Tsai CN, Lai MW, Chen CY, Lin KL, Lin TY, et al. 2009. Norovirus infection as a cause of diarrhea-associated benign infantile seizures. Clin. Infect. Dis. 48: 849-855.
Glass RI, Parashar UD, Estes MK. 2009. Norovirus gastroenteritis. N. Engl. J. Med. 361: 1776-1785.
Chan MC, Sung JJ, Lam RK, Chan PK, Lee NL, Lai RW, et al. 2006. Fecal viral load and norovirus-associated gastroenteritis. Emerg. Infect. Dis. 12: 1278-1280.
Matthews J, Dickey B, Miller R, Felzer J, Dawson B, Lee A, et al. 2012. The epidemiology of published norovirus outbreaks: a review of risk factors associated with attack rate and genogroup. Epidemiol Infect. 140: 1161-1172.
Kim HS, Hyun J, Kim HS, Kim JS, Song W, Lee KM. 2013. Emergence of GII. 4 Sydney norovirus in South Korea during the winter of 2012-2013. J. Microbiol. Biotechnol. 23:1641-1643.
Lee GC, Kim Mj, Kim JI, Lee CH. 2014. Occurrence and molecular characterization of noroviruses in Korean surface water between 2007 and 2010. J. Microbiol. Biotechnol. 24:556-562.
Atmar RL, Bernstein DI, Harro CD, Al-Ibrahim MS, Chen WH, Ferreira J, et al. 2011. Norovirus vaccine against experimental human Norwalk Virus illness. N. Engl. J. Med. 365: 21782187.
Luo K, Oh DH. 2015. Synergistic effect of slightly acidic electrolyzed water and ultrasound at mild heat temperature in microbial reduction and shelf-life extension of fresh-cut bell pepper. J. Microbiol. Biotechnol. 25: 1502-1509.
Kim EJ, Lee YD, Kim KY, Park JH. 2015. A synergy effect of trisodium phosphate and ethanol on inactivation of Murine Norovirus 1 on lettuce and bell pepper. J. Microbiol. Biotechnol. 25: 2106-2109.
Herbst-Kralovetz MM, Radtke AL, Lay MK, Hjelm BE, Bolick AN, Sarker SS, et al. 2013. Lack of norovirus replication and histo-blood group antigen expression in 3dimensional intestinal epithelial cells. Emerg. Infect. Dis. 19:431-438.
Straub TM, Zu Bentrup KH, Coghlan PO, Dohnalkova A, Mayer BK, Bartholomew RA, et al. 2007. In vitro cell culture infectivity assay for human noroviruses. Emerg. Infect. Dis. 13: 396-403.
Meurens F, Summerfield A, Nauwynck H, Saif L, Gerdts V. 2012. The pig: a model for human infectious diseases. Trends Microbiol. 20: 50-57.
Cheetham S, Souza M, Meulia T, Grimes S, Han MG, Saif LJ. 2006. Pathogenesis of a genogroup II human norovirus in gnotobiotic pigs. J. Virol. 80: 10372-10381.
Saif L, Ward L, Yuan L, Rosen B, To T. 1996. The gnotobiotic piglet as a model for studies of disease pathogenesis and immunity to human rotaviruses. Arch. Virol. Suppl. 12: 153-161.
Bui T, Kocher J, Li Y, Wen K, Li G, Liu F, et al. 2013. Median infectious dose of human norovirus GII. 4 in gnotobiotic pigs is decreased by simvastatin treatment and increased by age. J. Gen. Virol. 94: 2005-2016.
Ettayebi K, Crawford SE, Murakami K, Broughman JR, Karandikar U, Tenge VR, et al. 2016. Replication of human noroviruses in stem cell–derived human enteroids. Science 353: 1387-1393.
Karandikar UC, Crawford SE, Ajami NJ, Murakami K, Kou B, Ettayebi K, et al. 2016. Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients. J. Gen. Virol. 97: 2291-2300.
Karst SM, Wobus CE. 2015. A working model of how noroviruses infect the intestine. PLoS Pathog. 11: e1004626.
Gonzalez-Hernandez MB, Liu T, Blanco LP, Auble H, Payne HC, Wobus CE. 2013. Murine norovirus transcytosis across an in vitro polarized murine intestinal epithelial monolayer is mediated by M-like cells. J. Virol. 87: 12685-12693.
Green KY. 2016. Editorial commentary: Noroviruses and b cells. Clin. Infect. Dis. 62: 1139-1140.
Jones MK, Grau KR, Costantini V, Kolawole AO, De Graaf M, Freiden P, et al. 2015. Human norovirus culture in B cells. Nat. Protoc. 10: 1939-1947.
Jones MK, Watanabe M, Zhu S, Graves CL, Keyes LR, Grau KR, et al. 2014. Enteric bacteria promote human and mouse norovirus infection of B cells. Science 346: 755-759.
Wobus C E, T hackray L B, V irg ni HW. 2006. M urine norovirus: a model system to study norovirus biology and pathogenesis. J. Virol. 80: 5104-5112.
Wobus CE, Karst SM, Thackray LB, Chang K-O, Sosnovtsev SV, Belliot G, et al. 2004. Replication of Norovirus in cell culture reveals a tropism for dendritic cells and macrophages. PLoS Biol. 2: e432.
Seo DJ, Jung D, Jung S, Ha SK, Ha SD, Choi IS, et al. 2018. Experimental miniature piglet model for the infection of human norovirus GII. J. Med. Virol. 90: 655-662.
Le Guyader FS, Parnaudeau S, Schaeffer J, Bosch A, Loisy F, Pommepuy M, et al. 2009. Detection and quantification of noroviruses in shellfish. Appl. Environ. Microbiol. 75: 618-624.
Kageyama T, Shinohara M, Uchida K, Fukushi S, Hoshino FB, Kojima S, et al. 2004. Coexistence of multiple genotypes, including newly identified genotypes, in outbreaks of gastroenteritis due to Norovirus in Japan. J. Clin. Microbiol. 42: 2988-2995.
Seo K, Lee JE, Lim MY, Ko G. 2012. Effect of temperature, pH, and NaCl on the inactivation kinetics of murine norovirus. J. Food Prot. 75: 533-540.
Huang P, Farkas T, Marionneau S, Zhong W, RuvoënClouet N, Morrow AL, et al. 2003. Noroviruses bind to human ABO, Lewis, and secretor histo-blood group antigens:identification of 4 distinct strain-specific patterns. J. Infect. Dis. 188: 19-31.
Cheetham S, Souza M, McGregor R, Meulia T, Wang Q, Saif L. 2007. Binding patterns of human norovirus-like particles to buccal and intestinal tissues of gnotobiotic pigs in relation to A/H histo-blood group antigen expression. J. Virol. 81:3535-3544.
Marionneau S, Ruvoën N, Le Moullac–Vaidye B, Clement M, Cailleau–Thomas A, Ruiz–Palacois G, et al. 2002. Norwalk virus binds to histo-blood group antigens present on gastroduodenal epithelial cells of secretor individuals. Gastroenterology 122: 1967-1977.
Bok K, Parra GI, Mitra T, Abente E, Shaver CK, Boon D, et al. 2010. Chimpanzees as an animal model for human norovirus infection and vaccine development. Proc. Nat. Acad. Sci. USA 108: 325-330.
Perry JW, Taube S, Wobus CE. 2009. Murine norovirus-1 entry into permissive macrophages and dendritic cells is pH-independent. Virus Res. 143: 125-129.
Lei S, Ryu J, Wen K, Twitchell E, Bui T, Ramesh A, et al. 2016. Increased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency. Sci. Rep. 6: 25222.