Experimental infection of <i>Macaca nemestrina</i> with a Toronto Norwalk‐like virus of epidemic viral gastroenteritis

Subekti, Decy; Tjaniadi, Periska; Lesmana, Murad; McArdle, James L.; Iskandriati, Diah; Budiarsa, I Nengah; Walujo, P.; Suparto, Irma Herawati; Winoto, Imelda; Campbell, James; Porter, Kevin R.; Sajuthi, Dondin; Ansari, Aftab A.; Oyofo, Buhari A.

doi:10.1002/jmv.2159

Cited by 49 publications

(46 citation statements)

References 15 publications

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“…In this study, 65% of the HuNoV-HS66-infected pigs that were euthanized at PID 21 or PID 28 seroconverted with either IgA, IgG, or both, and coproconversion with either IgA or IgG antibodies was detected in 9/14 (64%) of the IC from the HuNoV-HS66-infected pigs tested. Similar results were observed in studies that used primates as experimental animal models, where some animals that shed Torontolike virus in the feces seroconverted and others did not (34).…”

Section: Discussionsupporting

confidence: 86%

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

Souza

Cheetham

Azevedo

et al. 2007

J Virol

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Section: Discussionsupporting

confidence: 86%

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

Souza

Cheetham

Azevedo

et al. 2007

J Virol

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“…In this study, ELISA, RT-PCR, and amplicon hybridization results varied from animal to animal, similarly to what has been previously described by others when inoculating monkeys with the NoV GII/3 Toronto strain (45). Therefore, all three tests were necessary to ensure viral detection.…”

Section: Discussionsupporting

confidence: 71%

“…By IEM, only a few viral particles were detected in only 1 of 15 pigs' intestinal contents tested at PID 3, indicative of very low concentrations of virus shedding (Ͻ10 6 viral particles/ml). Shedding of low quantities of virus has also been reported for humans and monkeys (45).…”

Section: Discussionmentioning

confidence: 97%

“…The antibody responses in humans may be of higher magnitude because, although long-term memory may not be as efficient in NoV infections as for other diseases and complete protection does not exist between strains from different genogroups (24), there are common epitopes within and between genogroups (33) that likely cause a stronger immune response after repeated NoV exposure. (45) and Rhesus monkeys inoculated with Norwalk virus where infection occurred in both the presence and absence of seroconversion (6). In another study where three Rhesus monkeys were inoculated with Norwalk virus, only the monkey that shed virus for 19 days seroconverted to Norwalk virus whereas the other two monkeys that shed for 1 to 2 days did not (39).…”

Section: Discussionmentioning

confidence: 99%

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Pathogenesis of a Genogroup II Human Norovirus in Gnotobiotic Pigs

Cheetham

Souza

Meulia

et al. 2006

J Virol

258

264

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Human noroviruses (HuNoVs) are a major cause of foodborne gastroenteritis worldwide. Because they do not grow in cell culture and there is no animal model for HuNoVs, pathogenesis studies have been hampered. Thus, little is known about their replication strategies or induction of neutralizing antibodies.The limited information on their pathogenesis is from human volunteer studies of HuNoV infections in which villus atrophy in duodenal biopsies and presence of malabsorptive diarrhea were described (1,7,8). No information is available on lesions in other portions of the intestines of these volunteers (9). Intestinal transplant pediatric patients that were diagnosed with HuNoV infection developed secretory or osmotic diarrhea (19,20,31). These patients had prolonged diarrhea (17 to 326 days) due to immunosuppressive therapy. The detection of HuNoV RNA and the clinical symptoms remitted after reduction of the immunosuppressive therapy. Usually in exposed individuals, histologic lesions correlate with diarrhea, but in one report, lesions in volunteers who did not show clinical symptoms were described (42). There are also numerous reports of asymptomatic individuals who were infected with HuNoVs and shed virus in the feces (11, 28).Most past attempts to study these viruses in an animal model may have failed because (i) the human strains that were used were not closely related to the host animal NoV strains, (ii) sensitive detection techniques were lacking, and finally (iii) the role of histo-blood group antigen (HBGA) phenotypes in differential susceptibility of the host was unrecognized. Our goal was to adapt a HuNoV strain to replicate in the gnotobiotic (Gn) pig to develop an animal model for the study of HuNoV pathogenesis. Gnotobiotic pigs are good models for human enteric diseases (40) because pigs resemble humans in their gastrointestinal anatomy, physiology, and immune responses. The Gn pigs are immunocompetent at birth, but they lack maternal antibodies and previous or ongoing exposure to microbial agents, including caliciviruses.Recently, viral RNA genetically similar to that of human NoV GII (65 to 71% amino acid sequence identity in the capsid gene) was detected in pigs in Japan (46, 47) and Europe (22,48). In U.S. swine, our laboratory detected both viral RNA and virus particles similar to GII HuNoV (70% sequence identity in the capsid region) which were infectious for Gn pigs (50). Our approach to infect Gn pigs with a HuNoV was to use a GII strain that is closely related genetically to the identified GII porcine NoVs and that has a broad HBGA binding pattern because little information or reagents are available for pig HBGA. Additionally, we used sensitive assays and reagents including reverse transcription (RT)-PCR to detect fecal shedding, virus-like particles (VLPs) for serological assays, and antisera to these VLPs for antigen enzyme-linked immunosor-

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“…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.

209

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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Experimental infection of Macaca nemestrina with a Toronto Norwalk‐like virus of epidemic viral gastroenteritis

Cited by 49 publications

References 15 publications

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

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

Pathogenesis of a Genogroup II Human Norovirus in Gnotobiotic Pigs

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

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