Cytokine and Antibody Responses in Gnotobiotic Pigs after Infection with Human Norovirus Genogroup II.4 (HS66 Strain)

Souza, Menira; Cheetham, Sonia; Azevedo, Marli S.P.; Costantini, Verónica; Saif, Linda J.

doi:10.1128/jvi.00558-07

Cited by 82 publications

(96 citation statements)

References 49 publications

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“…We also have recently delineated the immune responses to infection by the HuNoV-HS66 strain in Gn pigs (47). In this study we report the enteropathogenicity, viral shedding, and Ab and cytokine immune responses, both locally and systemically, of Gn calves experimentally infected with the HuNoV-HS66 strain and document the replication of HuNoV not only in Gn pigs as previously reported but also in Gn calves.…”

supporting

confidence: 77%

“…The numbers of ASC induced systemically (spleen and blood) in HuNoV-HS66-infected calves were generally low and similar to those in the Gn pigs infected with the HuNoV-HS66 strain (47), reflecting localized intestinal viral replication and transient viremia detectable in only one of the five HuNoV-HS66-inoculated calves but in 56% of the inoculated pigs. However, higher mean numbers of IgG ASC (77 ASC/5 ϫ 10 5 MNCs) were detected in the intestine of the HS66-inoculated calves at PID 28 than in the HuNoV-HS66-inoculated Gn pigs (4 ASC/5 ϫ 10 5 MNCs).…”

Section: Discussionmentioning

confidence: 69%

“…Animal models are important to study the pathogenesis and immune responses to enteric caliciviruses, and we previously described the detailed pathogenesis (10) and host immune responses of the HuNoV-HS66 strain in Gn pigs (47).…”

Section: Discussionmentioning

confidence: 99%

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Pathogenesis and Immune Responses in Gnotobiotic Calves after Infection with the Genogroup II.4-HS66 Strain of Human Norovirus

Souza

Azevedo

Jung

et al. 2008

J Virol

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150

131

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We previously characterized the pathogenesis of two host-specific bovine enteric caliciviruses (BEC), the GIII.2 norovirus (NoV) strain CV186-OH and the phylogenetically unassigned NB strain, in gnotobiotic (Gn) calves. In this study we evaluated the Gn calf as an alternative animal model to study the pathogenesis and host immune responses to the human norovirus (HuNoV) strain GII.4-HS66. The HuNoV HS66 strain caused diarrhea (five/five calves) and intestinal lesions (one/two calves tested) in the proximal small intestine (duodenum and jejunum) of Gn calves, with lesions similar to, but less severe than, those described for the Newbury agent 2 (NA-2) and NB BEC.

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supporting

confidence: 77%

Section: Discussionmentioning

confidence: 69%

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Pathogenesis and Immune Responses in Gnotobiotic Calves after Infection with the Genogroup II.4-HS66 Strain of Human Norovirus

Souza

Azevedo

Jung

et al. 2008

J Virol

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150

131

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“…Norovirus genome copies in biopsy samples from chimpanzee A2A014. The genome copies per 100 ng of total RNA in endoscope (duodenum, 11 dpi; jejunum, 21 dpi) and liver (7,14, and 21 dpi) biopsies are shown in relationship to the titer of norovirus shedding in stools.…”

Section: Resultsmentioning

confidence: 99%

“…Animal models have been actively sought for the study of norovirus pathogenesis and immunity, but each animal model has limitations in the study of human noroviruses, such as short-term shedding and variable immune responses (12)(13)(14)(15)(16). Challenge of nonhuman primates, such as rhesus macaques and newborn pigtail macaques, with human norovirus strains results in only sporadic asymptomatic infections (13,15).…”

mentioning

confidence: 99%

Chimpanzees as an animal model for human norovirus infection and vaccine development

Bok

Parra²,

Mitra³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

208

196

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Noroviruses are global agents of acute gastroenteritis, but the development of control strategies has been hampered by the absence of a robust animal model. Studies in chimpanzees have played a key role in the characterization of several fastidious hepatitis viruses, and we investigated the feasibility of such studies for the noroviruses. Seronegative chimpanzees inoculated i.v. with the human norovirus strain Norwalk virus (NV) did not show clinical signs of gastroenteritis, but the onset and duration of virus shedding in stool and serum antibody responses were similar to that observed in humans. NV RNA was detected in intestinal and liver biopsies concurrent with the detection of viral shedding in stool, and NV antigen expression was observed in cells of the small intestinal lamina propria. Two infected chimpanzees rechallenged 4, 10, or 24 mo later with NV were resistant to reinfection, and the presence of NV-specific serum antibodies correlated with protection. We evaluated the immunogenicity and efficacy of virus-like particles (VLPs) derived from NV (genogroup I, GI) and MD145 (genogroup II, GII) noroviruses as vaccines. Chimpanzees vaccinated intramuscularly with GI VLPs were protected from NV infection when challenged 2 and 18 mo after vaccination, whereas chimpanzees that received GII VLPs vaccine or a placebo were not. This study establishes the chimpanzee as a viable animal model for the study of norovirus replication and immunity, and shows that NV VLP vaccines could induce protective homologous immunity even after extended periods of time.

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Human Norovirus Detection and Production, Quantification, and Storage of Virus‐Like Particles

et al. 2013

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Human noroviruses constitute a significant worldwide disease burden. Each year, noroviruses cause over 267 million infections, deaths in over 200,000 children under the age of five, and over 50% of U.S. food-borne illness. Due to the absence of a tissue culture model or small animal model to study human norovirus, virus-like particles (VLPs) and ELISA-based biological assays have been used to answer questions about norovirus evolution and immunity as well to provide a potential vaccine platform. This chapter outlines the protocols for norovirus detection in stool, as well as norovirus VLP design, production, purification, and storage using a Venezuelan equine encephalitis virus (VEE)-based virus replicon particle (VRP) expression system.

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Cytokine and Antibody Responses in Gnotobiotic Pigs after Infection with Human Norovirus Genogroup II.4 (HS66 Strain)

Cited by 82 publications

References 49 publications

Pathogenesis and Immune Responses in Gnotobiotic Calves after Infection with the Genogroup II.4-HS66 Strain of Human Norovirus

Pathogenesis and Immune Responses in Gnotobiotic Calves after Infection with the Genogroup II.4-HS66 Strain of Human Norovirus

Chimpanzees as an animal model for human norovirus infection and vaccine development

Human Norovirus Detection and Production, Quantification, and Storage of Virus‐Like Particles

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