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PubMed2004

Prevalence of neutralizing antibodies against different rotavirus serotypes in children with severe rotavirus-induced diarrhea and their mothers.

Neutralizing antibody (NAb) responses to different rotavirus serotypes were compared in 64 convalescent-phase serum samples from hospitalized rotavirus-positive children less than 2 years of age and their mothers. Compared to the child patients, the mothers showed significantly higher NAb positivity to animal rotavirus serotypes G3 simian (96.88%), G6 bovine (85.94%), and G10 bovine (25.0%) and to human rotavirus serotypes G8 (79.69%) and G3 (57.81%) (P < 0.01 for each) but not to human serotypes G1, G2, G4, and G9 (P > 0.05). The overall prevalence of NAb among the child patients was low for human rotavirus serotypes G1 (20.31%) and G3 (21.8%). The comparative NAb response in individual mother-child paired serum samples was analyzed against each rotavirus serotype. A substantial number of child patients showed higher NAb titers than their mothers to serotypes G1, G2, G4, and G9, indicating that these serotypes are the major serotypes causing rotavirus diarrhea among the children of Pune, India. In these cases, the mothers were either negative or had lower titers of NAbs than their children. Correlation was observed between the infecting serotype and child patient serum that showed a homologous NAb response at a higher level than that of the mother. It appears that when the level of NAb to a particular serotype is higher among child patients than among their mothers, that serotype is the infecting serotype, and that low titers of NAb among the mothers predispose the children to infection with that serotype, if the serotype is in circulation.

Adult↗

PubMed1991

Reactivity of monoclonal antibodies to the 41-kilodalton protein of porcine group C rotavirus with homologous and heterologous rotavirus serogroups in immunofluorescence tests.

Three monoclonal antibodies (MAbs) to porcine group C rotavirus immunoprecipitated the major inner capsid protein (41 kDa) but failed to precipitate group A rotavirus proteins. In immunofluorescence tests of rotavirus-infected cell cultures or pig intestines, the MAbs recognized porcine and bovine group C rotaviruses but not group A or B rotaviruses. These MAbs may recognize the group C rotavirus counterpart to VP6 of group A rotaviruses and may be useful as diagnostic reagents.

Animals↗

PubMed1998

Rotavirus infection and rates of hospitalisation for acute gastroenteritis in young children in Australia, 1993-1996.

OBJECTIVE: To determine rates of hospitalisation of young children for acute gastroenteritis in Australia, and to estimate the proportion of these admissions caused by rotavirus infection. DESIGN: Analysis of hospital admission records, and parallel, prospectively collected data on rotavirus-positive admissions. SETTING: Hospitals admitting young children in all Australian States and Territories in 1993-1996. PATIENTS: All children under five years admitted to hospital for acute gastroenteritis (International Classification of Diseases, ninth revision principal diagnosis codes 003.0, 004.0-009.3 and 558.9). MAIN OUTCOME MEASURES: Rate of hospital admission per 1000 children per year by State, and the proportion of admissions caused by rotavirus infection. RESULTS: There were almost 20,000 hospital admissions annually in Australia for acute gastroenteritis in children under five years, at an average rate of 15/1000. An estimated 50% of these were attributable to rotavirus infection, implying a rate of hospitalisation for rotavirus-related gastroenteritis of 7.5/1000/year. Among children under two years this rate was 11.6/1000. Rotavirus incidence rates generally followed a typical seasonal pattern in temperate regions of the country, with sharp peaks in mid to late winter. Rates of hospitalisation varied markedly, even between States with apparently similar patterns of disease, while the incidence in the Northern Territory was 3-5 times higher than other States. CONCLUSIONS: Rotavirus-related gastroenteritis is a major cause of hospital admissions in young children, and large savings to the healthcare system are possible if it can be prevented at reasonable cost. Variation in treatment practices between States may be worth studying in greater detail as another source of potential savings.

Acute Disease↗

PubMed1984

[Comparative studies on the rotavirus syndrome following infection with human rotavirus of the subgroup 1 or 2].

Human rotavirus infection which heals spontaneously causes gastroenteritis in newborns and infants. 150 pediatric patients infected with rotavirus as diagnosed by ELISA suffered from diarrhoea for an average of 3 days, from vomiting for 1 day, and/or fever for 1-2 days. Nowadays this disease is known as "human rotavirus syndrome". Human rotaviruses can be divided into at least 4 serotype antigens and some 3 further subgroup antigens. The serotype antigens are only detectable biologically (e.g. by neutralization test), whereas the subgroup antigens can be demonstrated as specific proteins by a solid-phase test (ELISA). This study investigated whether an infection with human rotavirus of subgroup 1 (21%) or 2 (77%), which occur most frequently causes different degrees of severity of the rotavirus syndrome. The clinical comparison of 27 (subgroup 1) and 98 (subgroup 2) infected patients shows that the disease is not significantly different. This means that the detection of subgroup antigens 1 and 2 does not result in a different prognosis for the disease. The diagnosis of subgroup antigens after human rotavirus infection is therefore clinically important only for the detection of nosocomial infections, especially due to the rarely occurring subgroups 1 and 3.

Antigens, Viral↗

PubMed1983

Rotavirus associated diarrhoea in nursing piglets and detection of antibody against rotavirus in colostrum, milk and serum.

A blocking method of ELISA for the detection and quantification of antibody against porcine rotavirus in serum, colostrum and milk has been compared with a plaque reduction test. The results obtained with the two techniques correlated (Fig. 1). Antibody against rotavirus was demonstrated in 384 serum samples representing 25 swine farms, indicating a widely spread and dense distribution of the infection with porcine rotavirus among Danish swine. The antibody contents in milk samples from 7 gilts and sows from 2 farms with a previously diagnosed problem with rotavirus associated diarrhoe showed a rapid decline during the first few days of the lactation periods (Fig. 1). An increase in the contents of rotavirus specific antibody was observed from day 15 in the milk samples from one of the gilts. The excretion of rotavirus with feces from the 7 litters of piglets were followed through the suckling period. Rotavirus war found in all litters but one and the virus was excreted in periods ranging from 4 to 9 days.

Animal Population Groups↗

PubMed1981

Development of serum and intestinal antibody response to rotavirus after naturally acquired rotavirus infection in man.

The temporal characteristics of the response of rotavirus specific IgM, IgG, IgA in serum and secretory antibody in feces to rotavirus were studied in 77 hospitalized patients with rotavirus induced gastroenteritis. The response in serum was characterized by the sequential appearance of rotavirus specific IgM, IgG, and IgA antibody. The IgM antibody appeared to be higher in the acute phase of the disease and was subsequently replaced by the IgG and IgA antibodies. However, the titers of IgG rotavirus antibody in convalescent specimens of serum were found to be statistically significantly lower in patients with severe or prolonged rotavirus infection than in specimens from subjects with mild or moderate disease. Most fecal specimens collected during both the acute and convalescent phase of illness contained virus specific secretory IgA. Higher concentrations of antibody were measured in convalescent samples from patients with prolonged diarrhea and virus shedding. These observations suggest a possible relationship between the severity of rotavirus infection and the nature of systemic and secretory antibody response.

Antibodies, Viral↗

PubMed1996

Identification of a unique VP4 serotype that is shared by a human rotavirus (69M strain) and an equine rotavirus (H-2 strain).

A cDNA clone representing the VP4-encoding gene of human rotavirus strain 69M(VP7 serotype 8) was constructed and inserted into a baculovirus expression vector. Baculovirus recombinants that expressed the 69 M VP4 protein in Spodoptera frugiperda (Sf9) cells were screened by immunofluorescence with hyperimmune antiserum to the 69M strain and purified by terminal dilution. The expressed VP4 was detected by Coomassie blue staining of PAGE-separated proteins. The antigenic relationships between the VP4 of the 69M strain and those of various human and other animal rotavirus strains representing ten established VP4 serotypes were examined by plaque reduction neutralization. Hyperimmune antiserum produced in guinea pigs following immunization with a lysate of Sf9 cells infected with a 69M gene 4-baculovirus recombinant neutralized the infectivity of the homologous human rotavirus 69M strain as well as heterologous equine rotavirus H-2 strain to a high titer. The anti-69M VP4 hyperimmune antiserum did not neutralize significantly other rotavirus strains of human, simian, porcine, bovine, or murine origin. It thus appears that the human rotavirus 69M strain has a distinct VP4 serotype (designated as P serotype 4) which is closely related antigenically to equine rotavirus H-2 VP4.

Animals↗

PubMed2002

Human group C rotavirus: completion of the genome sequence and gene coding assignments of a non-cultivatable rotavirus.

Genome segments 1 and 2 of human group C rotavirus 'Bristol' strain were sequenced and their gene-protein coding properties assigned. This work completed the genome sequence of a human group C rotavirus (17,910 bp) and allowed the full gene-protein coding assignment of the 11 segments of dsRNA. Gene 1 is 3309 bp in size and contains a single ORF of 3272 nucleotides, encoding a protein of 1090 amino acids in length with a predicted molecular mass of 125 kDa. Comparison of the translated sequence with cognate published mammalian group A, B and C rotavirus sequences showed 45.2, 26.4 and 92.6% identity, respectively. The sequence contains conserved amino acid motifs including the classic RNA-dependent RNA polymerase motif GDD, indicating that segment 1 encodes the group C rotavirus polymerase protein. Gene 2 is 2736 bp in size and contains a single ORF of 2655 nucleotides encoding a protein of 884 amino acids in length with a calculated molecular mass of 102 kDa. Database searches showed highest homology with VP2, the main structural component of the 'core' from group A rotaviruses (46% identity). Alignment of the human group C and A rotavirus VP2 proteins revealed several characteristics common to nucleic acid binding proteins. However, these features were not shared with group B rotavirus VP2.

Amino Acid Sequence↗

PubMed1985

Reassortment of human rotaviruses carrying rearranged genomes with bovine rotavirus.

Rotaviruses isolated from chronically infected immunodeficient children were previously shown to contain RNA yielding abnormal migration profiles on gels: normal RNA segments were lost or decreased in concentration, and additional bands of dsRNA were found which were derived (rearranged) from genome segments of lower molecular weight by concatemer formation. These viruses grew very slowly during passage in secondary rhesus monkey kidney cells. Upon superinfection with the tissue culture-adapted UK Compton strain of bovine rotavirus (BRV) extensive genome reassortment occurred. Clones with the following reassorted genome patterns were isolated: (i) RNA segments 5 or 6 of BRV were replaced by the corresponding RNA segments of human rotavirus; (ii) RNA segments 9 or 11 of BRV were replaced by different rearranged bands of RNA of human rotavirus; (iii) reassortants were observed containing more than one segment/rearranged band of human rotavirus RNA in different combinations. The reassortant viruses possessed functional proteins coded for by the genome segments and/or by rearranged bands of RNA of the human rotaviruses. Rearrangement of parts of the rotavirus genome may be a mechanism of evolution of these viruses.

Animals↗

PubMed1983

Induction of cross-reactive serum neutralizing antibody to human rotavirus in calves after in utero administration of bovine rotavirus.

Sera from calves infected in utero or postnatally with bovine rotavirus NCDV or postnatally with human rotavirus D (serotype 1) were tested by plaque reduction neutralization assay for antibody to bovine rotavirus and to three serotypes of human rotavirus. Homologous antibody developed in all animals, but antibody to heterologous rotaviruses developed mainly in animals exposed in utero to bovine rotavirus. The development of heterologous antibody may explain the immunological implications for cross-protection, previously observed between bovine and human rotavirus in experimentally infected calves.

Animals↗

PubMed2003

Molecular analysis of the VP7, VP4, VP6, NSP4, and NSP5/6 genes of a buffalo rotavirus strain: identification of the rare P[3] rhesus rotavirus-like VP4 gene allele.

We report the detection and molecular characterization of a rotavirus strain, 10733, isolated from the feces of a buffalo calf affected with diarrhea in Italy. Strain 10733 was classified as a P[3] rotavirus, as the VP8* trypsin cleavage product of the VP4 protein revealed a high amino acid identity (96.2%) with that of rhesus rotavirus strain RRV (P5B[3]), used as the recipient virus in the human-simian reassortant vaccine. Analysis of the VP7 gene product revealed that strain 10733 possessed G6 serotype specificity, a type common in ruminants, with an amino acid identity to G6 rotavirus strains ranging from 88 to 98%, to Venezuelan bovine strain BRV033, and Hungarian human strain Hun4. Phylogenetic analysis based on the VP7 gene of G6 rotaviruses identified at least four lineages and an apparent linkage between each lineage and the VP4 specificity, suggesting the occurrence of repeated interspecies transmissions and genetic reassortment events between ruminant and human rotaviruses. Moreover, strain 10733 displayed a bovine-like NSP4 and NSP5/6 and a subgroup I VP6 specificity, as well as a long electropherotype pattern. The detection of the rare P[3] genotype in ruminants provides additional evidence for the wide genetic and antigenic diversity of group A rotaviruses.

Alleles↗

PubMed1989

RNA-RNA hybridization identifies a human rotavirus that is genetically related to feline rotavirus.

A human rotavirus AU228 strain which resembled the AU-1 strain (O. Nakagomi, T. Nakagomi, Y. Hoshino, J. Flores, and A. Z. Kapikian, J. Clin. Microbiol. 25:1159-1164, 1987) in its novel characteristics (that it belonged to subgroup I yet possessed a long RNA pattern) was compared with various human and animal strains by RNA-RNA hybridization in solution. This strain showed a high degree of homology with the AU-1 strain but not with either the Wa (subgroup II, long pattern) or the KUN (subgroup I, short pattern) strain, indicating the presence of an additional group of human rotaviruses that do not belong to either of the two human rotavirus families previously identified by RNA-RNA hybridization. It is of particular interest that the AU228 strain showed an unexpectedly high degree of homology with a feline rotavirus isolated recently in Japan. These results indicate transmission of a feline rotavirus to humans and suggest a role of animal rotaviruses in the evolution of human rotaviruses.

Animals↗

PubMed2006

Dissecting rotavirus particle-raft interaction with small interfering RNAs: insights into rotavirus transit through the secretory pathway.

Studies of rotavirus morphogenesis, transport, and release have shown that although these viruses are released from the apical surface of polarized intestinal cells before cellular lysis, they do not follow the classic exocytic pathway. Furthermore, increasing evidence suggests that lipid rafts actively participate in the exit of rotavirus from the infected cell. In this study, we silenced the expression of VP4, VP7, and NSP4 by using small interfering RNAs (siRNAs) and evaluated the effect of shutting down the expression of these proteins on rotavirus-raft interactions. Silencing of VP4 and NSP4 reduced the association of rotavirus particles with rafts; in contrast, inhibition of VP7 synthesis slightly affected the migration of virions into rafts. We found that inhibition of rotavirus migration into lipid rafts, by either siRNAs or tunicamycin, also specifically blocked the targeting of VP4 to rafts, suggesting that the association of VP4 with rafts is mostly mediated by the formation of viral particles in the endoplasmic reticulum (ER). We showed that two populations of VP4 exist, one small population that is independently targeted to rafts and a second large pool of VP4 whose association with rafts is mediated by particle formation in the ER. We also present evidence to support the hypothesis that assembly of VP4 into mature virions takes place in the late stages of transit through the ER. Finally, we analyzed the progression of rotavirus proteins in the exocytic pathway and found that VP4 and virion-assembled VP7 colocalized with ERGIC-53, suggesting that rotavirus particles transit through the intermediate compartment between the ER and the Golgi complex.

Animals↗

PubMed2002

Genetic analysis of Group A rotaviruses: evidence for interspecies transmission of rotavirus genes.

Rotaviruses are the major cause of severe gastroenteritis in young children and animals. The rotavirus genome is composed of eleven segments of double-stranded RNA and can undergo genetic reassortment during mixed infections, leading to progeny viruses with novel or atypical phenotypes. There are numerous descriptions of rotavirus strains isolated from human and animals that share genetic and antigenic features of viruses from heterologous species. In many cases, genetic analysis by hybridization has clearly demonstrated the genetic relatedness of gene segments to those from viruses isolated from different species. Together with the observation that some virus strains appear to have been transmitted to a different species as a whole genome constellation, these data suggest that interspecies transmission occurs naturally, albeit at low frequencies. Although interspecies transmission has not been documented directly, there is an increasing number of reports of atypical rotaviruses that are apparently derived from transmission between: humans, cats and dogs; humans and cattle; humans and pigs; pigs and cattle; and pigs and horses. Interspecies evolutionary relationships are supported by phylogenetic analysis of rotavirus genes from different species. The emergence of novel strains derived from interspecies transmission has implications for the design and implementation of successful human rotavirus vaccine strategies.

Animals↗

PubMed2005

Incidence of severe rotavirus diarrhea in New Delhi, India, and G and P types of the infecting rotavirus strains.

A total of 62,475 children <5 years old from a defined population of approximately 500,000 children and adults from slums in New Delhi, India, were assessed for 1 year by means of passive surveillance, to identify children who were hospitalized for diarrhea. The incidence of severe rotavirus diarrhea was estimated, and the G and P types of the infecting rotavirus strains were determined and were correlated with the clinical severity of diarrhea. Of 584 children who were hospitalized with diarrhea, 137 (23.5%) had rotavirus detected in stool specimens (incidence of rotavirus diarrhea-associated hospitalizations, 337 hospitalizations/100,000 children <5 years of age). Most cases of diarrhea (98%) occurred during the first 2 years of life, peaking at 9-11 months of age. Rotavirus-associated diarrhea occurred year-round but was predominant in winter. Among the strains that could be G-typed, G1 was the most common serotype, followed by G9 and G2; 10% of cases of diarrhea were due to mixed G-type infections. Common strains identified in the present surveillance study were P[8]G1, P[4]G2, P[8]G9, P[6]G1, P[6]G9, and P[6]G3. Children infected with G1 strains had a greater risk of developing more-severe cases of diarrhea than did children infected with other rotavirus strains (odds ratio, 2.95; 95% confidence interval, 1.3-6.67).

Adult↗

PubMed1992

Field trial of rhesus rotavirus or human-rhesus rotavirus reassortant vaccine of VP7 serotype 3 or 1 specificity in infants. The Elmwood, Panorama, and Westfall Pediatric Groups.

Orally administered live rhesus monkey rotavirus vaccine (RRV, VP7 serotype 3) and human-rhesus reassortant rotavirus vaccine (DxRRV, VP7 serotype 1) were evaluated in a placebo-controlled field trial of 223 infants 2-4 months old. Both vaccines were mildly reactogenic but were generally well tolerated in the 10 days after vaccination. RRV and DxRRV were immunogenic, inducing serum antibody responses in 78% and 71% of the vaccines, respectively. Efficacy of RRV vaccine was 66% (P = .01) and of DxRRV vaccine 77% (P = .002) against rotavirus-associated illness in the first season after vaccination. Efficacy of RRV vaccine against rotavirus-associated illness over three rotavirus seasons was 51.2% (P = .045) and of DxRRV vaccine was 67.3% (P = .006). RRV vaccine provided heterotypic protection of 58.5% (P = .041) and DxRRV vaccine provided homotypic protection of 72.8% (P = .005) over three seasons against the predominant serotype 1 rotavirus.

Administration, Oral↗

PubMed2006

The new pentavalent rotavirus vaccine composed of bovine (strain WC3) -human rotavirus reassortants.

BACKGROUND: Infantile gastroenteritis caused by human rotaviruses is a prevalent disease throughout the world, causing dehydration and hospitalization in all countries. In developing countries, it is associated with a high mortality. A licensed vaccine against rotavirus was withdrawn because of a causal association with intussusception. A new vaccine has been developed and is a candidate for licensure. METHODS: To recount the early development and recent demonstration of the safety and efficacy of the new vaccine. A bovine rotavirus attenuated for humans was isolated and reassorted with human rotaviruses of serotypes G1-4 and P1 to create a pentavalent vaccine. Multiple placebo-controlled clinical trials, including one involving approximately 70,000 infants, were conducted in multiple developed countries. RESULTS: The pentavalent vaccine was well tolerated by infants less than 8 months of age, and the incidence of intussusception was similar among vaccine and placebo recipients. More than 90% of infants had a significant rise in serum antirotavirus IgA titer after 3 doses. Efficacy of 95% against severe disease causing hospitalization or emergency care was demonstrated, and pentavalent vaccine prevented 74% of all rotavirus disease. CONCLUSIONS: If widely used, pentavalent vaccine would control rotavirus disease in the United States and other developed countries and could also have a major effect in developing countries.

Animals↗

PubMed1988

Asymptomatic excretion of rotavirus before and after rotavirus diarrhea in children in day care centers.

A 12-month prospective study of diarrhea in children in day care centers (DCCs) provided an opportunity to evaluate the duration of excretion of rotavirus from children before and after episodes of diarrhea caused by rotavirus. Ninety-nine episodes of rotavirus diarrhea occurred in 94 children. Asymptomatic rotavirus excretion occurred in 50% of children tested on the day before diarrhea occurred, 31% two days before diarrhea, and 9% in days 3 through 5 before diarrhea. Two children had positive specimens 11 and 13 days, respectively, before illness. During the week after cessation of diarrhea, 32% had positive specimens; 12% had positive stool specimens during the second week after diarrhea episodes. Electrophoretic testing of rotavirus RNA from stool specimens showed different electrophoretic migration patterns of the genomic RNA among the pairs tested, but the genomic RNA was the same within each pair of symptomatic and asymptomatic specimens. Excretion of rotavirus before and after diarrhea is common in children in DCCs; the role that asymptomatic excretion plays in the spread of this disease within DCCs is unknown.

Child Day Care Centers↗