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008200131s2018 ||||||||||||||||| ||eng d
020 ▼a 9781687927965
035 ▼a (MiAaPQ)AAI27536143
035 ▼a (MiAaPQ)umichrackham002220
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 247004
0820 ▼a 576.6
1001 ▼a Turula, Holly.
24510 ▼a Natural Secretory Immunoglobulins Facilitate Enteric Viral Infection.
260 ▼a [S.l.]: ▼b University of Michigan., ▼c 2018.
260 1 ▼a Ann Arbor: ▼b ProQuest Dissertations & Theses, ▼c 2018.
300 ▼a 182 p.
500 ▼a Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
500 ▼a Advisor: Moore, Bethany B.
5021 ▼a Thesis (Ph.D.)--University of Michigan, 2018.
506 ▼a This item must not be sold to any third party vendors.
506 ▼a This item must not be added to any third party search indexes.
520 ▼a Noroviruses are enteric pathogens causing significant morbidity, mortality and economic losses worldwide. Secretory immunoglobulins (SIg) are a first line of mucosal defense against enteric pathogens. They are secreted into the intestinal lumen via the polymeric immunoglobulin receptor (pIgR), where they bind to antigens. However, whether natural SIg protect against norovirus infection remains unknown. To determine if natural SIg alter murine norovirus (MNV) pathogenesis, I infected pIgR knockout (KO) mice, which lack SIg in mucosal secretions. Acute MNV infection was significantly reduced in pIgR KO mice compared to controls, despite increased MNV target cells in the Peyer's patch. Natural SIg did not alter MNV binding to, or crossing, of the follicle-associated epithelium (FAE) into the lymphoid follicle. Instead, naive pIgR KO mice have enhanced levels of the antiviral inflammatory molecules interferon gamma (IFN-g) and inducible nitric oxide synthase (iNOS) in the ileum compared to controls. Strikingly, depletion of the intestinal microbiota in pIgR KO and control mice resulted in comparable IFN-g and iNOS levels, as well as MNV infectious titers. IFN-g treatment of WT mice and neutralization of IFN-g in pIgR KO mice modulated MNV titers, implicating this antiviral cytokine in the phenotype. Reduced gastrointestinal infection in pIgR KO mice was also observed with another enteric virus, reovirus. Collectively, my findings suggest that natural SIg are not protective during enteric virus infection, but rather that SIg promote enteric viral infection through alterations in microbial immune responses.
590 ▼a School code: 0127.
650 4 ▼a Epidemiology.
650 4 ▼a Immunology.
650 4 ▼a Virology.
690 ▼a 0982
690 ▼a 0720
690 ▼a 0766
71020 ▼a University of Michigan. ▼b Immunology.
7730 ▼t Dissertations Abstracts International ▼g 81-05B.
773 ▼t Dissertation Abstract International
790 ▼a 0127
791 ▼a Ph.D.
792 ▼a 2018
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15494205 ▼n KERIS ▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다.
980 ▼a 202002 ▼f 2020
990 ▼a ***1008102
991 ▼a E-BOOK