Rotavirus vaccines and pathogenesis: 2008

Hyser, Joseph M.; Estes, Mary K.

doi:10.1097/mog.0b013e328317c897

Cited by 38 publications

(33 citation statements)

References 51 publications

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“…Rotaviruses are etiological agents of severe dehydrating diarrhea in infants and young children and cause nearly 600,000 deaths globally every year (34). Rotaviruses are nonenveloped icosahedral members of the family Reoviridae and contain 11 segments of genomic double-stranded RNA (dsRNA) within a triple-layered particle.…”

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confidence: 99%

The Early Interferon Response to Rotavirus Is Regulated by PKR and Depends on MAVS/IPS-1, RIG-I, MDA-5, and IRF3

Pruijssers

Dermody

et al. 2011

J Virol

134

136

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In mouse embryonic fibroblasts (MEFs), the bovine rotavirus (UK strain) but not the simian rhesus rotavirus (RRV) robustly triggers beta interferon (IFN-␤Rotaviruses are etiological agents of severe dehydrating diarrhea in infants and young children and cause nearly 600,000 deaths globally every year (34). Rotaviruses are nonenveloped icosahedral members of the family Reoviridae and contain 11 segments of genomic double-stranded RNA (dsRNA) within a triple-layered particle. Several rotavirus vaccines have been developed to reduce rotavirus-associated mortalities (26); some are based on a modified Jennerian principle of rotavirus attenuation in the heterologous host. This phenomenon is termed host range restriction and is manifested by poor replication of rotaviruses in heterologous hosts compared to that in the homologous host (1). For example, bovine, lapine, and simian rotaviruses are all restricted for replication in humans. We are interested in understanding the mechanisms underlying host range restriction of rotaviruses in order to improve our basic knowledge of viral pathogenesis and because of the importance of these mechanisms in rational attenuation of vaccine candidates.In primary mouse embryonic fibroblasts (MEFs), several heterologous (nonmurine) rotavirus strains, including the bovine UK strain, are replication restricted by the host type I interferon (IFN) response (17, 53). In contrast, replication of homologous murine EW virus and the heterologous simian rhesus rotavirus (RRV) strain is insensitive to the presence of the interferon system. In a mouse model of rotavirus infection, RRV replication in gallbladder epithelia correlates with its ability to suppress the IFN response (N. Feng et al., submitted for publication). The rotavirus gene segment encoding the nonstructural protein 1 (NSP1) is an important determinant of host restriction of viral replication both in vitro (17,53) and in vivo (9). Specifically, we along with others have reported a role for NSP1 in regulating the ability of rotavirus to efficiently cause diarrhea in mice (9), spread from animal to animal (9), replicate in vivo and in vitro (4,(15)(16)(17), and antagonize IFN (4,5,17,24,25,53). Thus, the host innate immune response is an important determinant of rotavirus host range restriction and depends on both the virus strain and host cell or tissue type.Mammalian innate immunity to viral infection is critically dependent on a successful type I IFN response (49). The early IFN response involves initial recognition of virus within infected cells by activation of host pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs)

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confidence: 99%

The Early Interferon Response to Rotavirus Is Regulated by PKR and Depends on MAVS/IPS-1, RIG-I, MDA-5, and IRF3

Pruijssers

Dermody

et al. 2011

J Virol

134

136

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“…14 subsequently vaccines such as Rota Teq and Rotarix have been developed. 15 The Clinical Presentation having typical triad of severe intermittent abdominal pain, currant jelly stools and vomiting is seen in less than 20% of cases. 16 Bouts of abdominal pain may be evidenced by pulling of knees against the abdomen with an interim asymptomatic healthy child.…”

Section: Discussionmentioning

confidence: 99%

Current Trends in Paediatric Intususceptions

M¹,

Basawaraj²,

Tulsi³

et al. 2015

jemds

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Intussusception is the major cause of acute intestinal obstruction in infants. The classic clinical triad of intussusception is colicky abdominal pain, vomiting and bloody stools. However, only 20% of patients present with this triad. OBJECTIVES: The objective of this article with a series of cases of intussusception is to review the spectrum of clinical presentation of this disease entity and also to study the effectiveness of non-surgical intervention in children with intussusception using barium enema reduction under fluoroscopy. METHODS AND RESULTS: This prospective study spread over a period of 3 year and six months from October 2010 to march 2014 was carried out in tertiary care hospital in south Bangalore. Complete review of medical records for clinical and demographic information was only performed for those cases fulfilling diagnostic certainty (Definite intussusception). During the surveillance period, A total of 40 patients, diagnosed cases were included in this study. The majority (78.4%) of the cases occurred in the first year of life. The male: female ratio was 2.4: 1. Intussusception cases occurred round the year with no distinct seasonality. No intussusception-associated death was recorded. Cases identified in the study were similar in presentation and demographics as those observed in other south East Asian settings. Clinical presentation of the patients were pain abdomen, vomiting, blood in stools, fever and loose stools. Among the patients who were admitted the time between the onset of symptoms and hospitalization was between 36 to 48 hours, After stabilizing them haemodynamically they were subjected to definitive procedure, Barium enema reduction was tried in all patients, exclusion criteria was patients with clinical and radiological sign and symptoms of peritonitis, duration of symptoms more than 30hours and massive abdominal distension. Out of forty cases, thirty seven (81.8%) were reduced by fluoroscopic guided barium enema, those who failed among them, one (2.5) was reduced by pneumatic reduction, one (2.5) was reduced by ultrasound guided pneumatic reduction and only one (2.5%) patient required surgical interventions, reduced manually during surgery. No mortalities were recorded during the study. There was one recurrence noted in our study 15 days after discharge and was subsequently treated with fluoroscopic guided contrast reduction. CONCLUSION: Surgical intervention in intussusception can be prevented by non-operative reduction especially if presented early and no signs of peritonitis.

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“…Here, expression of the rotavirus enterotoxin (NSP4) was carried out before and after removal of its diarrhea-inducing domain in E. coli BL21 DE3. As this protein is made of different domains with distinct functions (3), it has been subject of different studies in full-length, modified, truncated, and mutated forms (5,9,17,21). This protein is toxic for both prokaryotic and eukaryotic (especially mammalian) cells because of disruption of calcium homeostasis and membrane destabilization (29,35).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the integrins α1β1 and α2β1 are receptors for NSP4 in which amino acids 114-130 are responsible for binding to the I domain of α1; and residues 114-135 can block binding of the natural ligand, collagen I, to Integrin α2 (8). This interaction in turn leads to secretion of chloride ions and diarrhea-induction via a phospholipase C (PLC) mediated pathway (9). Therefore, it can be suggested that removing amino acids 114-135 could effectively lower, if not inhibit, the toxicity of NSP4 for two reasons: first, via disrupting the correct functional conformation and oligomerization of the protein and second, via blocking the interaction of NSP4 with integrin receptors.…”

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confidence: 99%