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PLoS Pathogens Jan 2013Viral pathogens must overcome innate antiviral responses to replicate successfully in the host organism. Some of the mechanisms viruses use to interfere with antiviral... (Review)
Review
Viral pathogens must overcome innate antiviral responses to replicate successfully in the host organism. Some of the mechanisms viruses use to interfere with antiviral responses in the infected cell include preventing detection of viral components, perturbing the function of transcription factors that initiate antiviral responses, and inhibiting downstream signal transduction. RNA viruses with small genomes and limited coding space often express multifunctional proteins that modulate several aspects of the normal host response to infection. One such virus, rotavirus, is an important pediatric pathogen that causes severe gastroenteritis, leading to ~450,000 deaths globally each year. In this review, we discuss the nature of the innate antiviral responses triggered by rotavirus infection and the viral mechanisms for inhibiting these responses.
Topics: Gastroenteritis; Host-Pathogen Interactions; Humans; Immunity, Innate; Interferons; Rotavirus; Rotavirus Infections; Signal Transduction
PubMed: 23359266
DOI: 10.1371/journal.ppat.1003064 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jul 2017Rotaviruses are leading causes of worldwide acute diarrhea in children younger than 5 years old, with severe consequence of social and economic burden. Vaccination is... (Review)
Review
Rotaviruses are leading causes of worldwide acute diarrhea in children younger than 5 years old, with severe consequence of social and economic burden. Vaccination is the most effective way to control rotavirus infection, however, the licensed rotavirus vaccines are ineffective in some low-income countries of Africa and Asia, where the mortality caused by rotavirus is higher than other areas. In addition, there are also safety concerns such as increased risk of intussusception. Therefore, it is urgent to improve the efficiency and safety of rotavirus vaccine to reduce the morbidity and mortality caused by rotavirus. Till now, many efforts are made to improve the effectiveness of rotavirus vaccines, and the inactive vaccine becomes the main trend in the research of rotavirus vaccine. The developments in recombinant rotavirus vaccines, especially in VP4 subunit vaccines are summarized in this review, and it could be helpful to develop effective recombinant rotavirus vaccines in further studies.
Topics: Diarrhea; Humans; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Subunit
PubMed: 28869727
DOI: 10.13345/j.cjb.160480 -
Philosophical Transactions of the Royal... Oct 2003The rich epidemiological database of the incidence of rotavirus, as a cause of severe diarrhoea in young children, coupled with knowledge of the natural history of the... (Review)
Review
The rich epidemiological database of the incidence of rotavirus, as a cause of severe diarrhoea in young children, coupled with knowledge of the natural history of the infection, can make this virus a paradigm for studies of epidemic dynamics. The cyclic recurrence of childhood rotavirus epidemics in unvaccinated populations provides one of the best documented phenomena in population dynamics. This paper makes use of epidemiological data on rotavirus infection in young children admitted to hospital in Melbourne, Australia from 1977 to 2000. Several mathematical methods were used to characterize the overall dynamics of rotavirus infections as a whole and individually as serotypes G1, G2, G3, G4 and G9. These mathematical methods are as follows: seasonal autoregressive integrated moving-average (SARIMA) models, power spectral density (PSD), higher-order spectral analysis (HOSA) (bispectrum estimation and quadratic phase coupling (QPC)), detrended fluctuation analysis (DFA), wavelet analysis (WA) and a surrogate data analysis technique. Each of these techniques revealed different dynamic aspects of rotavirus epidemiology. In particular, we confirm the existence of an annual, biannual and a quinquennial period but additionally we found other embedded cycles (e.g. ca. 3 years). There seems to be an overall unique geometric and dynamic structure of the data despite the apparent changes in the dynamics of the last years. The inherent dynamics seems to be conserved regardless of the emergence of new serotypes, the re-emergence of old serotypes or the transient disappearance of a particular serotype. More importantly, the dynamics of all serotypes is multiple synchronized so that they behave as a single entity at the epidemic level. Overall, the whole dynamics follow a scale-free power-law fractal scaling behaviour. We found that there are three different scaling regions in the time-series, suggesting that processes influencing the epidemic dynamics of rotavirus over less than 12 months differ from those that operate between 1 and ca. 3 years, as well as those between 3 and ca. 5 years. To discard the possibility that the observed patterns could be due to artefacts, we applied a surrogate data analysis technique which enabled us to discern if only random components or linear features of the incidence of rotavirus contribute to its dynamics. The global dynamics of the epidemic is portrayed by wavelet-based incidence analysis. The resulting wavelet transform of the incidence of rotavirus crisply reveals a repeating pattern over time that looks similar on many scales (a property called self-similarity). Both the self-similar behaviour and the absence of a single characteristic scale of the power-law fractal-like scaling of the incidence of rotavirus infection imply that there is not a universal inherently more virulent serotype to which severe gastroenteritis can uniquely be ascribed.
Topics: Australia; Child; Disease Outbreaks; Humans; Longitudinal Studies; Models, Theoretical; Periodicity; Population Dynamics; Rotavirus Infections
PubMed: 14561323
DOI: 10.1098/rstb.2003.1291 -
Gut Microbes Sep 2020Multiple studies have identified changes within the gut microbiome in response to diarrheal-inducing bacterial pathogens. However, examination of the microbiome in...
Multiple studies have identified changes within the gut microbiome in response to diarrheal-inducing bacterial pathogens. However, examination of the microbiome in response to viral pathogens remains understudied. Compounding this, many studies use fecal samples to assess microbiome composition; which may not accurately mirror changes within the small intestine, the primary site for most enteric virus infections. As a result, the functional significance of small intestinal microbiome shifts during infection is not well defined. To address these gaps, rotavirus-infected neonatal mice were examined for changes in bacterial community dynamics, host gene expression, and tissue recovery during infection. Profiling bacterial communities using 16S rRNA sequencing suggested significant and distinct changes in ileal communities in response to rotavirus infection, with no significant changes for other gastrointestinal (GI) compartments. At 1-d post-infection, we observed a loss in species from the ileum, but an increase in and , both of which exhibit mucin-digesting capabilities. Concomitant with the bacterial community shifts, we observed a loss of mucin-filled goblet cells in the small intestine at d 1, with recovery occurring by d 3. Rotavirus infection of mucin-producing cell lines and human intestinal enteroids (HIEs) stimulated release of stored mucin granules, similar to findings. , incubation of mucins with or members resulted in significant glycan degradation, which altered the binding capacity of rotavirus and . Taken together, these data suggest that the response to and recovery from rotavirus-diarrhea is unique between sub-compartments of the GI tract and may be influenced by mucin-degrading microbes.
Topics: Akkermansia; Animals; Animals, Newborn; Bacteria; Bacteroides; Gastrointestinal Microbiome; Goblet Cells; Ileum; Intestine, Small; Lactobacillus; Mice; Mice, Inbred BALB C; Mucins; Polysaccharides; RNA, Ribosomal, 16S; Rotavirus; Rotavirus Infections; Virulence
PubMed: 32404017
DOI: 10.1080/19490976.2020.1754714 -
PLoS Computational Biology Jul 2019Cohort studies, randomized trials, and post-licensure studies have reported reduced natural and vaccine-derived protection against rotavirus gastroenteritis (RVGE) in...
Cohort studies, randomized trials, and post-licensure studies have reported reduced natural and vaccine-derived protection against rotavirus gastroenteritis (RVGE) in low- and middle-income countries. While susceptibility of children to rotavirus is known to vary within and between settings, implications for estimation of immune protection are not well understood. We sought to re-estimate naturally-acquired protection against rotavirus infection and RVGE, and to understand how differences in susceptibility among children impacted estimates. We re-analyzed data from studies conducted in Mexico City, Mexico and Vellore, India. Cumulatively, 573 rotavirus-unvaccinated children experienced 1418 rotavirus infections and 371 episodes of RVGE over 17,636 child-months. We developed a model that characterized susceptibility to rotavirus infection and RVGE among children, accounting for aspects of the natural history of rotavirus and differences in transmission rates between settings. We tested whether model-generated susceptibility measurements were associated with demographic and anthropometric factors, and with the severity of RVGE symptoms. We identified greater variation in susceptibility to rotavirus infection and RVGE in Vellore than in Mexico City. In both cohorts, susceptibility to rotavirus infection and RVGE were associated with male sex, lower birth weight, lower maternal education, and having fewer siblings; within Vellore, susceptibility was also associated with lower socioeconomic status. Children who were more susceptible to rotavirus also experienced higher rates of rotavirus-negative diarrhea, and higher risk of moderate-to-severe symptoms when experiencing RVGE. Simulations suggested that discrepant estimates of naturally-acquired immunity against RVGE can be attributed, in part, to between-setting differences in susceptibility of children, but result primarily from the interaction of transmission rates with age-dependent risk for infections to cause RVGE. We found that more children in Vellore than in Mexico City belong to a high-risk group for rotavirus infection and RVGE, and demonstrate that unmeasured individual- and age-dependent susceptibility may influence estimates of naturally-acquired immune protection against RVGE.
Topics: Child, Preschool; Cohort Studies; Disease Susceptibility; Female; Gastroenteritis; Humans; Infant; Infant, Newborn; Male; Mexico; Risk Factors; Rotavirus Infections
PubMed: 31348775
DOI: 10.1371/journal.pcbi.1007014 -
The Journal of Infectious Diseases Jul 2014Rotavirus causes 500 000 deaths and millions of physician visits and hospitalizations per year, with worse outcomes and reduced vaccine efficacy in developing countries....
BACKGROUND
Rotavirus causes 500 000 deaths and millions of physician visits and hospitalizations per year, with worse outcomes and reduced vaccine efficacy in developing countries. We hypothesized that the gut microbiota might modulate rotavirus infection and/or antibody response and thus potentially play a role in such regional differences.
METHODS
The microbiota was ablated via germ-free or antibiotic approaches. Enhanced exposure to microbiota was achieved via low-dose dextran sodium sulfate (DSS) treatment. Rotavirus infection and replication was assessed by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse-transcription polymerase chain reaction. Diarrhea was scored visually. Humoral responses to rotavirus were measured by ELISA and enzyme-linked immunosorbent spot assay.
RESULTS
Microbiota elimination delayed infection and reduced infectivity by 42%. Antibiotics did not alter ratios of positive-sense to negative-sense strands, suggesting that entry rather than replication was influenced. Antibiotics reduced the diarrhea incidence and duration, indicating that the reduction in the level of rotavirus antigen was biologically significant. Despite lowered antigen level, antibiotics resulted in a more durable rotavirus mucosal/systemic humoral response. Increased rotavirus antibody response durability correlated with increased small intestinal rotavirus-specific, immunoglobulin A-producing antibody-secreting cell concentration in antibiotic-treated mice. Conversely, DSS treatment impaired generation of rotavirus-specific antibodies.
CONCLUSIONS
Microbiota ablation resulted in reduced rotavirus infection/diarrhea and a more durable rotavirus antibody response, suggesting that antibiotic administration before rotavirus vaccination could raise low seroconversion rates that correlate with the vaccine's inefficacy in developing regions.
Topics: Animals; Anti-Bacterial Agents; Antibodies, Viral; Diarrhea; Enzyme-Linked Immunosorbent Assay; Female; Gastrointestinal Tract; Immunity, Humoral; Male; Mice; Mice, Inbred C57BL; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Rotavirus; Rotavirus Infections; Viral Load
PubMed: 24436449
DOI: 10.1093/infdis/jiu037 -
Human Vaccines & Immunotherapeutics Sep 2016Rotavirus (RV) is worldwide considered as the most important viral agent of acute gastroenteritis in children less than 5 y. Since 2006, the availability of anti-RV... (Review)
Review
Rotavirus (RV) is worldwide considered as the most important viral agent of acute gastroenteritis in children less than 5 y. Since 2006, the availability of anti-RV vaccines has deeply modified the incidence and economic burden of RV infection. In Europe, some countries have introduced an anti-RV vaccination program in the last 10 y. Although community acquired RV (CARV) disease is the most studied condition of RV infection, recently some authors have highlighted the importance of nosocomial RV (nRV) disease as an emerging public health issue. The aim of this review is to summarize the epidemiology of both CARV and nRV, in order to discuss the difficulty of a clear evaluation of the burden of the disease in absence of comparable data. In particular, we focused our attention to European studies regarding nRV in terms of divergences related to definition, report of incidence rate and methodological issues.
Topics: Community-Acquired Infections; Cost of Illness; Cross Infection; Europe; Gastroenteritis; Humans; Rotavirus Infections
PubMed: 27185183
DOI: 10.1080/21645515.2016.1183858 -
Viruses Oct 2022Rotavirus (RV) is a non-enveloped icosahedral virus with an 11-segment double-stranded RNA genome, belonging to the family of rotaviruses. RV is one of the pathogens...
Rotavirus (RV) is a non-enveloped icosahedral virus with an 11-segment double-stranded RNA genome, belonging to the family of rotaviruses. RV is one of the pathogens causing diarrhea in infants and young animals, and it induces the production of type I interferons (IFNs), which can trigger antiviral function by inducing the production of interferon-stimulated genes (ISGs). Although IFITM3, an ISG localizing to late endosomes, can limit many viral infections, whether or not it restricts the infection of RV is still unknown. Therefore, we attempted to determine whether IFITM3 also restricts RV infection by using over-expression and knockout cell strains. It was found that IFITM3-expressing cell strains were less susceptible to RV infection, as the replication of RV in over-expressing cells was significantly less than in control group cells. Correspondingly, IFITM3-knockout cells were significantly susceptible compared to the normal cells. Furthermore, the IFN-induced antiviral effect was significantly attenuated in the absence of IFITM3, and IFITM3 delayed RV escape from endosomes in the presence of IFITM3, suggesting that endogenous IFITM3 is of great importance in type I IFN-mediated antiviral responses and may restrict infection by affecting the function of the late endosomal compartment. In conclusion, these data provide the first evidence that IFITM3 limits RV infection in vitro and delays RV escape from late endosomes into the cytoplasm.
Topics: Animals; Rotavirus Infections; Membrane Proteins; Rotavirus; Antiviral Agents; Interferon Type I; Virus Replication
PubMed: 36366505
DOI: 10.3390/v14112407 -
PloS One 2020Rotavirus infection is the most common cause of viral diarrhea in infants and young children but uncommon and usually asymptomatic in adults. In the winter of 2017-2018,...
Rotavirus infection is the most common cause of viral diarrhea in infants and young children but uncommon and usually asymptomatic in adults. In the winter of 2017-2018, a large-scale outbreak of rotavirus in both children and adults was reported in Thailand. The current study focused on the prevalence, genotyping, and molecular characterization of rotavirus infections in Thai adults from July 2016 to December 2019. In 2,598 stool samples collected from adult residents of Bangkok (aged #x2265; 15 years) with acute gastroenteritis, rotavirus was detected via real-time RT-PCR analysis of the VP6 gene. G, P and I genotypes were determined by direct sequencing of VP7, VP4, and VP6 genes, respectively. Our results showed 8.7% (226/2,598) of stool samples were positive for rotavirus. The incidence of rotavirus was high during the winter season of 2017-2018 (17.7%) compared to another studied periods (4.5% between July 2016- October 2017 and 2.8% between March 2018- December 2019). Nucleotide sequencing of VP7 and VP4 revealed G3P[8] as the predominant strain (33.2%,75/226), followed by G9P[8] (17.3%,39/226), and G2P[4] (15.0%,34/226). Uncommon G and P combinations were additionally detected at low frequencies. VP6 sequencing was conducted to discriminate I genotype between the Wa and DS-1 genogroup. The unusual DS-1-like G3P[8] strain was most prevalent amomg rotavirus strains detected in this study (29.6%, 67/226), and the corresponding VP7 sequences showed high nucleotide identity with unusual DS-1-like globally circulating strains. Our study demonstrates that rotavirus outbreaks in adults are attributable not only to high prevalence of RV infection but also the unusual DS-like genogroup. The collective findings reinforce the importance of investigating rotavirus diagnosis in adults suffering from acute gastroenteritis and taking appropriate preventive measures.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Viral; Capsid Proteins; Feces; Female; Genotype; Humans; Male; Middle Aged; Phylogeny; Prevalence; RNA, Viral; Rotavirus; Rotavirus Infections; Thailand; Young Adult
PubMed: 32584905
DOI: 10.1371/journal.pone.0235280 -
Srpski Arhiv Za Celokupno Lekarstvo 2006Rotavirus is the main etiological agent that causes severe diarrheal diseases in newborns and young children up to two years. Every year, about one million children... (Review)
Review
Rotavirus is the main etiological agent that causes severe diarrheal diseases in newborns and young children up to two years. Every year, about one million children around the globe die of dehydration caused by Rotaviruses. The problem is even bigger in underdeveloped and developing countries. The results of our 18-month research, in the town Kragujevac and its surrounding area from December 1998 to May 2000 indicate that viruses are an important factor in the etiology of the acute diarrheal diseases in our population. In 124 children, aged 0 to 5, with the acute diarrheal diseases treated at the Pediatric clinic HMC "Kragujevac", viruses were the causes in 27% of the time. The Rotavirus belongs to the family Reoviridae. The infections caused by rotaviruses may be detected around the world. The incidence rate is higher in developed countries. The infection is transmitted orally. The entry of the Rotavirus infection is the upper part of the small intestine. The clinical picture is specific. The disease usually lasts four to seven days. The fastest diagnostic method is direct detection of viruses using the electronic microscope. The agglutination tests ELISA and LATEX are used for the examination of numerous samples. Only symptomatic treatment is required. High morbidity and mortality rates in developing countries are the reason to prevent the Rotavirus disease by active immunization.
Topics: Child, Preschool; Diarrhea, Infantile; Gastroenteritis; Humans; Infant; Rotavirus Infections
PubMed: 16915761
DOI: No ID Found