A Mouse-Adapted Enterovirus 71 Strain Causes Neurological Disease in Mice after Oral Infection
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Published in | Journal of Virology Vol. 78; no. 15; pp. 7916 - 7924 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Washington, DC
American Society for Microbiology
01.08.2004
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AbstractList | ABSTRACT
A mouse-adapted enterovirus 71 (EV71) strain with increased virulence in mice, MP4, was generated after four serial passages of the parental EV71 strain 4643 in mice. Strain MP4 exhibited a larger plaque size, grew more rapidly, and was more cytotoxic in vitro than strain 4643. Although strains 4643 and MP4 both induced apoptosis of SK-N-SH human neuroblastoma cells, MP4 was more virulent than 4643 in 1-day-old mice (50% lethal doses, 10
2
and 10
4
PFU/mouse, respectively). Strain MP4 (5 × 10
6
PFU/mouse), but not 4643, could orally infect 7-day-old mice, resulting in rear-limb paralysis followed by death 5 to 9 days after inoculation with the virus. Histopathologically, neuronal loss and apoptosis were evident in the spinal cords as well as the brain stems of the infected mice. The limb muscles displayed massive necrosis. There was early and transient virus replication in the intestines, whereas the spinal cord, brain, and muscle became the sites of viral replication during the late phase of the infection. Virus transmission occurred among infected and noninfected cagemates, as demonstrated by the occurrence of seroconversion and the presence of viable viruses in the stool samples of the latter. Protection against EV71 challenge was demonstrated following administration of hyperimmune serum 1 day after inoculation with the virus. Nucleotide sequence analysis of the genome of EV71 strain MP4 revealed four nucleotide changes on the 5′ untranslated region, three on the VP2 region, and eight on the 2C region, resulting in one and four amino acid substitutions in the VP2 and 2C proteins, respectively. A mouse-adapted enterovirus 71 (EV71) strain with increased virulence in mice, MP4, was generated after four serial passages of the parental EV71 strain 4643 in mice. Strain MP4 exhibited a larger plaque size, grew more rapidly, and was more cytotoxic in vitro than strain 4643. Although strains 4643 and MP4 both induced apoptosis of SK-N-SH human neuroblastoma cells, MP4 was more virulent than 4643 in 1-day-old mice (50% lethal doses, 10(2) and 10(4) PFU/mouse, respectively). Strain MP4 (5 x 10(6) PFU/mouse), but not 4643, could orally infect 7-day-old mice, resulting in rear-limb paralysis followed by death 5 to 9 days after inoculation with the virus. Histopathologically, neuronal loss and apoptosis were evident in the spinal cords as well as the brain stems of the infected mice. The limb muscles displayed massive necrosis. There was early and transient virus replication in the intestines, whereas the spinal cord, brain, and muscle became the sites of viral replication during the late phase of the infection. Virus transmission occurred among infected and noninfected cagemates, as demonstrated by the occurrence of seroconversion and the presence of viable viruses in the stool samples of the latter. Protection against EV71 challenge was demonstrated following administration of hyperimmune serum 1 day after inoculation with the virus. Nucleotide sequence analysis of the genome of EV71 strain MP4 revealed four nucleotide changes on the 5' untranslated region, three on the VP2 region, and eight on the 2C region, resulting in one and four amino acid substitutions in the VP2 and 2C proteins, respectively. Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI A mouse-adapted enterovirus 71 (EV71) strain with increased virulence in mice, MP4, was generated after four serial passages of the parental EV71 strain 4643 in mice. Strain MP4 exhibited a larger plaque size, grew more rapidly, and was more cytotoxic in vitro than strain 4643. Although strains 4643 and MP4 both induced apoptosis of SK-N-SH human neuroblastoma cells, MP4 was more virulent than 4643 in 1-day-old mice (50% lethal doses, 10 2 and 10 4 PFU/mouse, respectively). Strain MP4 (5 × 10 6 PFU/mouse), but not 4643, could orally infect 7-day-old mice, resulting in rear-limb paralysis followed by death 5 to 9 days after inoculation with the virus. Histopathologically, neuronal loss and apoptosis were evident in the spinal cords as well as the brain stems of the infected mice. The limb muscles displayed massive necrosis. There was early and transient virus replication in the intestines, whereas the spinal cord, brain, and muscle became the sites of viral replication during the late phase of the infection. Virus transmission occurred among infected and noninfected cagemates, as demonstrated by the occurrence of seroconversion and the presence of viable viruses in the stool samples of the latter. Protection against EV71 challenge was demonstrated following administration of hyperimmune serum 1 day after inoculation with the virus. Nucleotide sequence analysis of the genome of EV71 strain MP4 revealed four nucleotide changes on the 5′ untranslated region, three on the VP2 region, and eight on the 2C region, resulting in one and four amino acid substitutions in the VP2 and 2C proteins, respectively. A mouse-adapted enterovirus 71 (EV71) strain with increased virulence in mice, MP4, was generated after four serial passages of the parental EV71 strain 4643 in mice. Strain MP4 exhibited a larger plaque size, grew more rapidly, and was more cytotoxic in vitro than strain 4643. Although strains 4643 and MP4 both induced apoptosis of SK-N-SH human neuroblastoma cells, MP4 was more virulent than 4643 in 1-day-old mice (50% lethal doses, 10 super(2) and 10 super(4) PFU/mouse, respectively). Strain MP4 (5 x 10 super(6) PFU/mouse), but not 4643, could orally infect 7-day-old mice, resulting in rear-limb paralysis followed by death 5 to 9 days after inoculation with the virus. Histopathologically, neuronal loss and apoptosis were evident in the spinal cords as well as the brain stems of the infected mice. The limb muscles displayed massive necrosis. There was early and transient virus replication in the intestines, whereas the spinal cord, brain, and muscle became the sites of viral replication during the late phase of the infection. Virus transmission occurred among infected and noninfected cagemates, as demonstrated by the occurrence of seroconversion and the presence of viable viruses in the stool samples of the latter. Protection against EV71 challenge was demonstrated following administration of hyperimmune serum 1 day after inoculation with the virus. Nucleotide sequence analysis of the genome of EV71 strain MP4 revealed four nucleotide changes on the 5' untranslated region, three on the VP2 region, and eight on the 2C region, resulting in one and four amino acid substitutions in the VP2 and 2C proteins, respectively. |
Author | Shih-Min Wang Shun-Hua Chen Ya-Fang Wang Ching-Chuan Liu Ih-Jen Su Chun-Keung Yu Chun-Ting Chou Trai-Ming Yeh Jing-Jou Yan Huan-Yao Lei Jen-Reng Wang |
AuthorAffiliation | Institute of Basic Medical Sciences, 1 Departments of Microbiology and Immunology, 2 Pediatrics, 3 Pathology, 4 Clinical Medicine, 5 Medical Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China 6 |
AuthorAffiliation_xml | – name: Institute of Basic Medical Sciences, 1 Departments of Microbiology and Immunology, 2 Pediatrics, 3 Pathology, 4 Clinical Medicine, 5 Medical Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China 6 |
Author_xml | – sequence: 1 givenname: Ya-Fang surname: WANG fullname: WANG, Ya-Fang organization: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China – sequence: 2 givenname: Chun-Ting surname: CHOU fullname: CHOU, Chun-Ting organization: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China – sequence: 3 givenname: Chun-Keung surname: YU fullname: YU, Chun-Keung organization: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China – sequence: 4 givenname: Huan-Yao surname: LEI fullname: LEI, Huan-Yao organization: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China – sequence: 5 givenname: Ching-Chuan surname: LIU fullname: LIU, Ching-Chuan organization: Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China – sequence: 6 givenname: Shih-Min surname: WANG fullname: WANG, Shih-Min organization: Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China – sequence: 7 givenname: Jing-Jou surname: YAN fullname: YAN, Jing-Jou organization: Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China – sequence: 8 givenname: Ih-Jen surname: SU fullname: SU, Ih-Jen organization: Department of Clinical Medicine, Collegeof Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China – sequence: 9 givenname: Jen-Reng surname: WANG fullname: WANG, Jen-Reng organization: Department of Medical Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China – sequence: 10 givenname: Trai-Ming surname: YEH fullname: YEH, Trai-Ming organization: Department of Medical Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China – sequence: 11 givenname: Shun-Hua surname: CHEN fullname: CHEN, Shun-Hua organization: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Province of China |
BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15969826$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/15254164$$D View this record in MEDLINE/PubMed |
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Keywords | Picornaviridae Motor system disorder Size Virulence Central nervous system Enterovirus Neuroblastoma Limb Paralysis Neurological disorder Dose Human Nervous system diseases Digestive system Rodentia Oral administration Malignant tumor In vitro Strain Virus Infection Vertebrata Mammalia Mouse Cell death Animal Oral cavity disease Autonomic neuropathy Apoptosis |
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Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China. Phone: 886-6-2353535, ext. 5673. Fax: 886-6-2082705. E-mail: dckyu@mail.ncku.edu.tw. |
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PublicationTitle | Journal of Virology |
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Mendeley... A mouse-adapted enterovirus 71 (EV71) strain with increased virulence in mice, MP4, was generated after four serial passages of the parental EV71 strain 4643... ABSTRACT A mouse-adapted enterovirus 71 (EV71) strain with increased virulence in mice, MP4, was generated after four serial passages of the parental EV71... |
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SubjectTerms | 5' Untranslated Regions - chemistry Animals Antibodies, Viral - immunology Apoptosis Biological and medical sciences Central Nervous System Diseases - etiology Central Nervous System Diseases - pathology Enterovirus - pathogenicity Enterovirus 71 Enterovirus Infections - pathology Enterovirus Infections - virology Fundamental and applied biological sciences. Psychology Humans Medical sciences Mice Mice, Inbred ICR Microbiology Miscellaneous Pathogenesis and Immunity Tumors Virology Virulence Virus Replication |
Title | A Mouse-Adapted Enterovirus 71 Strain Causes Neurological Disease in Mice after Oral Infection |
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