Biological Properties of Norwalk Agent of Acute Infectious Nonbacterial Gastroenteritis

Dolin, Raphael; Blacklow, Neil R.; DuPont, Herbert L.; Buscho, Robert F.; Wyatt, Richard G.; Kasel, Julius A.; Hornick, Richard B.; Chanock, Robert M.

doi:10.3181/00379727-140-36508

Cited by 239 publications

(144 citation statements)

References 7 publications

(15 reference statements)

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“…In contrast, four of our 8 newborn infants with NV infection (50%) had bloody stools and one of them 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 10 had NEC [6]. Human noroviruses are thought to have an enteric tropism limited to the upper intestinal tract, because intestinal biopsies from volunteers revealed villous broadening and atrophy, crypt cell hyperplasia and cytoplasmic vacuolization in the jejunum and duodenum and an infiltration of polymorphonuclear and mononuclear cells into the lamina propria [28][29][30][31]. Similar pathology is seen in biopsies from pediatric transplant patients with diarrhea associated with human NV infection [32].…”

Section: Case Definitions and Laboratory Methods: Nec Was Staged Accomentioning

confidence: 99%

Clinical characteristics of viral intestinal infection in preterm and term neonates

Bağcı

Eis‐Hübinger

Yassin

et al. 2010

Eur J Clin Microbiol Infect Dis

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Objectives: The clinical presentation of the viral enteric pathogens in newborn infants has not been adequately examined. The aim of this study was to evaluate the clinical characteristics of viral intestinal infections in newborn infants. Methods: Clinical data of all term and preterm infants admitted to our tertiary neonatal intensive care unit from 1998 to 2007 with clinical signs of gastroenteritis (GE) or necrotizing enterocolitis (NEC) were retrospectively reviewed and compared between infants with different viral enteric pathogens in stool specimens. Results: In thirty-four infants with signs of GE or NEC, enteropathogenic viruses were found in stool specimens. Rotavirus was detected in 12 cases, of which 2 infants had NEC. Compared with infants with rotavirus or norovirus, infants with astrovirus more frequently suffered from NEC (p<0.05). In addition, an acute systemic inflammatory response was significantly more common in patients with astrovirus infection (astrovirus vs. rotavirus and astrovirus vs. norovirus p<0.01 and p<0.05, respectively). Of 8 children infected with norovirus, one infant had a systemic acute inflammatory response and NEC. Conclusions: This study demonstrates that in newborn infants, intestinal rotavirus, norovirus, and astrovirus infections may be associated with severe illness such as hemorrhagic enteritis resulting in bloody diarrhea or even NEC. We revised our manuscript "Clinical characteristics of viral intestinal infection in preterm and term neonates" according to the reviewers' comments. You may find our comments, additions and answers below (all changes made to the manuscript text are underlined).Reviewers' Comment 1: In the Abstract, under the Objectives paragraph it is stated that "The clinical presentation of viral intestinal infections in preterm and term neonates has not been adequately evaluated". This statement is not an objective in itself. It is an observation that could be included as background or as part of the introduction. The aims of the study should be better defined. Answer 1: According the reviewers' suggestions we revised the objectives in the abstract. Because of "200 words-limit in abstract" we revised the abstract, too (all changes made to the manuscript text are underlined).Reviewers' Comment 2: In the Results section (p.2, line 19) it should be mentioned that enteropathogenic viruses were found in 34 infants out of 220 (15.45%) infants with gastroenteritis (GE) and NEC (nectotizing enterocolitis). Answer 2: According the reviewers' suggestions we changed the sentence as recommended (Page 6, p.2).Reviewers' Comment 3: Among 112 infants with gastroenteritis, enteric viruses were detected in 22 patients (19.64%), and in 12 cases (11.11%) out of 108 infants with NEC. That means that approximately only in one case out of every 10 infants suffering of NEC was an enteric virus detected. The majority of cases with RV infection (10/12) were mild and self-limiting GE, but 2 preterm infants had signs of NEC. In this study, no enteric viruses were de...

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Section: Case Definitions and Laboratory Methods: Nec Was Staged Accomentioning

confidence: 99%

Clinical characteristics of viral intestinal infection in preterm and term neonates

Bağcı

Eis‐Hübinger

Yassin

et al. 2010

Eur J Clin Microbiol Infect Dis

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“…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).…”

mentioning

confidence: 99%

“…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).…”

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confidence: 99%

Pathogenesis of a Genogroup II Human Norovirus in Gnotobiotic Pigs

Cheetham

Souza

Meulia

et al. 2006

J Virol

257

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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“…This difference in sensitivity to low pH between FCV and MNV was suggested to be related with the different routes of infection of these viruses ). While MNV is an enteric virus that infects its host by the small intestine and retains infectivity for hours at a pH of 2 (similarly to the human Norwalk virus), FCV is a respiratory virus that significantly decreases infectivity at low pH (Cannon et al, 2006;Dolin et al, 1972).…”

Section: Targeting Entry and Uncoating Of Norovirusmentioning

confidence: 99%