동물 로타바이러스의 수용체 및 국내에서 호발하는 소 유전형에 대한 로타바이러스 백신 개발 Identification of animal rotavirus VP8* receptors and development of a live attenuated trivalent bovine rotavirus vaccine원문보기
김지윤
(Chonnam National University
Department of Veterinary Medicine
국내박사)
Group A Rotaviruses (RVAs) are the most common cause of severe diarrhea in children and young animals. They have been classified into at least nine groups (A-I) on the basis of the antigenic specificities of their VP6 capsid protein. RVA initiates the infection by interaction among VP8* domain of th...
Group A Rotaviruses (RVAs) are the most common cause of severe diarrhea in children and young animals. They have been classified into at least nine groups (A-I) on the basis of the antigenic specificities of their VP6 capsid protein. RVA initiates the infection by interaction among VP8* domain of the spike protein VP4 with cell surface carbohydrate moieties, SAs or HBGAs. RVAs are divided into neuraminidase (NA)-sensitive and NA-insensitive strains depending upon their binding affinity of the VP8* domain to the terminal SAs or histo-blood group antigens (HBGAs) of cell surface carbohydrates. Although NA-sensitive strains are known to use terminal SAs as an attachment factor, the exact nature of this attachment factor is largely unknown. This study demonstrated that four NA-sensitive animal strains could have a strain-dependent binding preference toward α2,6-linked SAs (P[1] NCDV and P[3] CU-1 strains) or both α2,3- and α2,6-linked SAs (P[7] PRG9121 and P[23] PRG942 strains) to the glycolipid and N-linked glycoprotein. Although bovine G6P[5] WC3 strain is an important animal pathogen and used for the bovine-human reassortant RotaTeq vaccine, the receptor for VP8* domain of both WC3 and its reassortant strains has remained elusive. The present HBGA- and saliva-binding assays showed that both G6P[5] WC3 and bovine-human reassortant G4P[5] strains recognized the αGal HBGA as a receptor. Contrary to previous results, the infectivity of both P[5] strains was significantly reduced in the αGal free MA-104 cells by pretreatment with a NA and Sambucus nigra lectin, suggesting that both P[5] strains could also utilize α2,6-linked SA as a receptor. These results demonstrated that both P[5] strains could utilize α2,6-linked SA and αGal HBGA as ligands. Infection of bovine RVAs (BRVAs) is the most common cause of acute viral gastroenteritis in neonatal calves worldwide. Therefore, effective BRVA vaccines are crucial to prevent morbidity and mortality of calves from BRVA infection. In this study, three Korean BRVA strains including KJ11(G8P[7]), KJ19-2 (G6P[7]), and KJ44 (G5P[1]) strains to be confirmed representative as the most prevalent strains were passaged 80 times in MA104 cells. All vaccine to be tested had no adverse reactions in vaccinated mice, guinea pigs, calves, and cows. Moreover, a live attenuated trivalent vaccine candidate did not cause diarrhea in any experimental calves during five consecutive passages in calves. An immunization of three live attenuated vaccine candidates and a live attenuated trivalent vaccine candidate into calves could protect the diarrhea and also alleviated fecal shedding and histopathological changes caused by the challenge of their counterpart original virulent strains. These protective effects of small intestine would be partially due to sufficient secretion of IgA into the feces. Consequently, three live attenuated monovalent vaccines and a trivalent vaccine are very effective and safe to protect the infection of each homologous virulent strain in calves. These studies provide a better understanding of the rotavirus-host susceptibility through identification of receptor for VP8* domain of animal rotavirus depends on P genogroup and development of efficient bovine rotavirus vaccine with the prevalent rotavirus genotypes in cattle.
Group A Rotaviruses (RVAs) are the most common cause of severe diarrhea in children and young animals. They have been classified into at least nine groups (A-I) on the basis of the antigenic specificities of their VP6 capsid protein. RVA initiates the infection by interaction among VP8* domain of the spike protein VP4 with cell surface carbohydrate moieties, SAs or HBGAs. RVAs are divided into neuraminidase (NA)-sensitive and NA-insensitive strains depending upon their binding affinity of the VP8* domain to the terminal SAs or histo-blood group antigens (HBGAs) of cell surface carbohydrates. Although NA-sensitive strains are known to use terminal SAs as an attachment factor, the exact nature of this attachment factor is largely unknown. This study demonstrated that four NA-sensitive animal strains could have a strain-dependent binding preference toward α2,6-linked SAs (P[1] NCDV and P[3] CU-1 strains) or both α2,3- and α2,6-linked SAs (P[7] PRG9121 and P[23] PRG942 strains) to the glycolipid and N-linked glycoprotein. Although bovine G6P[5] WC3 strain is an important animal pathogen and used for the bovine-human reassortant RotaTeq vaccine, the receptor for VP8* domain of both WC3 and its reassortant strains has remained elusive. The present HBGA- and saliva-binding assays showed that both G6P[5] WC3 and bovine-human reassortant G4P[5] strains recognized the αGal HBGA as a receptor. Contrary to previous results, the infectivity of both P[5] strains was significantly reduced in the αGal free MA-104 cells by pretreatment with a NA and Sambucus nigra lectin, suggesting that both P[5] strains could also utilize α2,6-linked SA as a receptor. These results demonstrated that both P[5] strains could utilize α2,6-linked SA and αGal HBGA as ligands. Infection of bovine RVAs (BRVAs) is the most common cause of acute viral gastroenteritis in neonatal calves worldwide. Therefore, effective BRVA vaccines are crucial to prevent morbidity and mortality of calves from BRVA infection. In this study, three Korean BRVA strains including KJ11(G8P[7]), KJ19-2 (G6P[7]), and KJ44 (G5P[1]) strains to be confirmed representative as the most prevalent strains were passaged 80 times in MA104 cells. All vaccine to be tested had no adverse reactions in vaccinated mice, guinea pigs, calves, and cows. Moreover, a live attenuated trivalent vaccine candidate did not cause diarrhea in any experimental calves during five consecutive passages in calves. An immunization of three live attenuated vaccine candidates and a live attenuated trivalent vaccine candidate into calves could protect the diarrhea and also alleviated fecal shedding and histopathological changes caused by the challenge of their counterpart original virulent strains. These protective effects of small intestine would be partially due to sufficient secretion of IgA into the feces. Consequently, three live attenuated monovalent vaccines and a trivalent vaccine are very effective and safe to protect the infection of each homologous virulent strain in calves. These studies provide a better understanding of the rotavirus-host susceptibility through identification of receptor for VP8* domain of animal rotavirus depends on P genogroup and development of efficient bovine rotavirus vaccine with the prevalent rotavirus genotypes in cattle.
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