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Thesis Yue Duan 4-17.pdf (2.9 MB)

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A cultivable primate calicivirus causes enteric infections in gnotobiotic piglets

Duan, Yue
http://rave.ohiolink.edu/etdc/view?acc_num=osu1366250409

Abstract Details

2013, Master of Science, Ohio State University, Food Science and Technology.
Many enteric caliciviruses cause acute gastroenteritis in humans and animals. Examples of these include human norovirus (NoV), human sapovirus, and the newly discovered recoviruses. It is estimated that human NoV accounts for over 95% of nonbacterial acute gastroenteritis worldwide. However, research efforts on enteric caliciviruses have been severely hampered primarily because many of these cannot be propagated in vitro. Tulane virus (TV), a newly discovered enteric primate calicivirus recovered from the feces of rhesus macaques, is cultivable and recognizes histo-blood group antigens (HBGAs) similar to human NoV. The objectives of this study are to determine (i)Whether the pathogenesis of TV can be recapitulated in gnotobiotic piglets, (ii)Whether TV can be adapted to pig macrophage cell line, (iii)Whether macrophage-adapted TV has altered virulence in piglets, and (iv)Whether TV can be passed repeatedly in piglets. To determine the pathogenesis of TV in gnotobiotic piglets, twenty-eight newborn gnotobiotic piglets were orally inoculated with 2×108 PFU of TV and euthanized at days post-inoculation (PID) 3,4,5,6, and 10. Twelve of the twenty-eight (43%) inoculated piglets developed mild diarrhea. Infectious virus was detected in stools on PIDs 1-5, but was undetectable beyond PID 6. Viral RNA was detectable through PIDs 1 to 10, and viral RNA level remained high for 10 days. Viral RNA was detected in the intestinal contents and intestine tissue segments of the duodenum, jejunum, and ileum on all PIDs, but infectious virus was detected only on PIDs 4 and 5. Piglets developed TV-neutralizing antibodies by PID 6. TV antigens were present in villus tip (epithelial) cells and cells within the lamina propria of the duodenum and jejunum only. Histologic examination demonstrated mild villous atrophy and increased numbers of mononuclear inflammatory cells in duodenal and jejunal tissues. These results demonstrated that TV caused mild enteritis, viral shedding, and intestinal histologic lesions similar to those described for TV in primates and human NoV in humans. To determine whether TV has a tropism for macrophages, a continuous swine macrophage cell line (3D/4) was infected with TV. It was found that TV caused typical cytopathic effects (CPE) and replicated efficiently in pig macrophages. To determine whether macrophage-adapted TV had altered virulence in vivo, 107 PFU of TV was inoculated into newborn gnotobiotic piglets. It was found that the macrophage cell-adapted TV caused low levels of viral and RNA shedding in feces but did not cause any histologic changes or antigen expression, suggesting the macrophage cell-adapted TV had reduced virulence in pigs. To determine whether TV can be passed in piglets, fecal samples were collected from TV-infected piglets and used for oral inoculation of naive piglets. Although histologic changes and TV antigens were not detectable in the intestine, fecal infiltrates containing 104 PFU of TV from TV-infected piglets can lead to viral shedding of 102.5 PFU/g feces for at least 4 days. Thus, it is promising to adapt TV in piglets by a serial of in vivo passage. Collectively, it was concluded that (i) TV, the only cultivable primate calicivirus, caused symptoms of enteritis and intestinal histologic lesions in gnotobiotic pigs and, (ii) TV has a tropism for porcine macrophages. These findings suggested that TV infection of gnotobiotic pigs can be used as a novel model to study the replication and pathogenesis of enteric caliciviruses in vivo.
Jianrong Li (Advisor)
Steven Krakowka (Committee Member)
Ahmed Yousef (Committee Member)
Food Science
Tulane virus; Recovirus; animal model; gnotobiotic pig; pathogenesis

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Citations

  • Duan, Y. (2013). A cultivable primate calicivirus causes enteric infections in gnotobiotic piglets [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366250409

    APA Style (7th edition)

  • Duan, Yue. A cultivable primate calicivirus causes enteric infections in gnotobiotic piglets. 2013. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1366250409.

    MLA Style (8th edition)

  • Duan, Yue. "A cultivable primate calicivirus causes enteric infections in gnotobiotic piglets." Master's thesis, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366250409

    Chicago Manual of Style (17th edition)

osu1366250409
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This open access ETD is published by The Ohio State University and OhioLINK.