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1.
Virology ; 598: 110195, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39089050

ABSTRACT

Rotavirus A is a leading cause of non-bacterial gastroenteritis in humans and domesticated animals. Despite the vast diversity of bovine Rotavirus A strains documented in South Asian countries, there are very few whole genomes available for phylogenetic study. A cross-sectional study identified a high prevalence of the G6P[11] genotype of bovine Rotavirus A circulating in the commercial cattle population in Bangladesh. Next-generation sequencing and downstream phylogenetic analysis unveiled all 11 complete gene segments of this strain (BD_ROTA_CVASU), classifying it under the genomic constellation G6P[11]-I2-R2-C2-M2-A13-N2-T6-E2-H3, which belongs to a classical DS-1-like genomic backbone. We found strong evidence of intragenic recombination between human and bovine strains in the Non-structural protein 4 (NSP4) gene, which encodes a multifunctional enterotoxin. Our analyses highlight frequent zoonotic transmissions of rotaviruses in diverse human-animal interfaces, which might have contributed to the evolution and pathogenesis of this dominant genotype circulating in the commercial cattle population in Bangladesh.


Subject(s)
Cattle Diseases , Genome, Viral , Genotype , Phylogeny , Recombination, Genetic , Rotavirus Infections , Rotavirus , Toxins, Biological , Viral Nonstructural Proteins , Animals , Cattle , Rotavirus/genetics , Rotavirus/classification , Rotavirus/isolation & purification , Bangladesh/epidemiology , Viral Nonstructural Proteins/genetics , Humans , Rotavirus Infections/virology , Rotavirus Infections/veterinary , Rotavirus Infections/epidemiology , Cattle Diseases/virology , Cattle Diseases/epidemiology , Cross-Sectional Studies , Toxins, Biological/genetics , Glycoproteins/genetics
2.
Virology ; 598: 110185, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39096775

ABSTRACT

Among group A rotaviruses (RVAs), the G1 genotype is the main genotype causing diarrhea in children, but it has rarely been reported in pigs. During our epidemiological investigation, we detected G1P[7] rotavirus infection in piglets across several provinces in China and then isolated a porcine G1P[7] rotavirus strain (CN1P7). Sequencing revealed that the virus constellation was G1-P[7]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Phylogenetic analyses revealed that CN1P7 most likely emerged due to genetic reassortment among porcine, human, giant panda and dog rotavirus strains. In vivo experiments were conducted on two-day-old piglets, which revealed that the CN1P7 strain was pathogenic to piglets. The virus was shed through the digestive tract and respiratory tract. In addition to the intestine, the CN1P7 strain displayed extraintestinal tropisms in piglets. Histopathological analysis revealed that the lung and small intestine were the targets of CN1P7. This study is the first to explore the molecular and pathogenic characterization of a pig-origin G1P[7] rotavirus.


Subject(s)
Genotype , Phylogeny , Rotavirus Infections , Rotavirus , Swine Diseases , Animals , Swine , Rotavirus Infections/virology , Rotavirus Infections/veterinary , Rotavirus/genetics , Rotavirus/classification , Rotavirus/isolation & purification , China/epidemiology , Swine Diseases/virology , Reassortant Viruses/genetics , Reassortant Viruses/pathogenicity , Genome, Viral
4.
Lancet Glob Health ; 12(9): e1517-e1525, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39151986

ABSTRACT

BACKGROUND: Afghanistan introduced monovalent rotavirus vaccine (Rotarix) into its national immunisation schedule in January, 2018. While post-licensure studies have shown substantial declines in rotavirus gastroenteritis cases and deaths globally, there is little evidence of rotavirus vaccine effectiveness and impact from low-income countries in Asia. We aimed to evaluate the effectiveness of the Rotarix vaccine and the impact of Rotarix vaccine on rotavirus gastroenteritis hospitalisations (ie, hospital admissions) among children younger than 5 years in Afghanistan. METHODS: We used a test-negative case-control design embedded in an active sentinel surveillance platform to evaluate vaccine effectiveness. Children born on or after Jan 1, 2018, who had documentation of their rotavirus vaccination status and who were admitted for acute gastroenteritis at one of four sentinel hospitals from May, 2018 to December, 2021 were eligible to be included. We used an unconditional logistic regression model to estimate vaccine effectiveness and 95% CIs for a complete series of doses compared with no rotavirus vaccine doses among patients admitted with acute gastroenteritis. Vaccine effectiveness against hospitalisation was calculated as (1 - [odds of being vaccinated in cases] / [odds of being vaccinated in controls]) × 100%. We compared pre-vaccine (2013-15) and post-vaccine (2019-21) surveillance data from two sites to calculate vaccine impact. FINDINGS: The vaccine effectiveness analysis included 1172 cases and 2173 controls. Approximately 2108 (63·0%) of 3345 cases and controls were male, 1237 (37·0%) were female, and 2171 (65·0%) were aged 6-11 months. Two doses of Rotarix were 45% (95% CI 22-62) effective against rotavirus hospitalisation in children aged 6-59 months, adjusting for age, severity, admission year, and rotavirus season. Rotavirus positivity decreased from 51% pre-vaccine to 39% post-vaccine, resulting in a 39% adjusted reduction in rotavirus positivity among children younger than 5 years admitted with acute gastroenteritis. INTERPRETATION: Rotarix showed moderate effectiveness in preventing rotavirus gastroenteritis hospitalisations, consistent with findings in other low-income countries. These findings support the continued administration of the rotavirus vaccine in Afghanistan. FUNDING: Gavi, the Vaccine Alliance. TRANSLATION: For the Dari translation of the abstract see Supplementary Materials section.


Subject(s)
Gastroenteritis , Rotavirus Infections , Rotavirus Vaccines , Vaccine Efficacy , Humans , Rotavirus Vaccines/administration & dosage , Rotavirus Infections/prevention & control , Rotavirus Infections/epidemiology , Afghanistan/epidemiology , Case-Control Studies , Infant , Male , Female , Child, Preschool , Gastroenteritis/prevention & control , Gastroenteritis/virology , Gastroenteritis/epidemiology , Vaccine Efficacy/statistics & numerical data , Vaccines, Attenuated/administration & dosage , Hospitalization/statistics & numerical data , Sentinel Surveillance , Vaccination/statistics & numerical data
5.
BMC Infect Dis ; 24(1): 836, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39152402

ABSTRACT

BACKGROUND: Rotavirus infections are a significant cause of severe diarrhea and related illness and death in children under five worldwide. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in high deaths annually, mainly in low-income countries, including Ethiopia, and need special attention. This system review and meta-analysis aimed to comprehensively explore the positive proportion of rotavirus at pre- and post-vaccine introduction periods and genotype distribution in children under five with diarrhea in Ethiopia. METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Database sources included PubMed, Scopus, EMBASE, and Epistemonikos, focusing on studies published before November 30, 2023. The search targeted rotavirus infection and genotype distribution in Ethiopia before and after the introduction of the Rota vaccine. Data was managed using EndNote 2020 software and stored in an Excel 2010 sheet. A random-effects model determined the pooled estimate of the rotavirus infection rate at 95% confidence intervals. The Q-and I² statistics were used to assess the study heterogeneity, and a funnel plot (Egger test) was used to determine the possibility of publication bias. RESULTS: The analysis included data from nine studies conducted in different regions of Ethiopia. The overall prevalence of rotavirus infection was significant, with a prevalence rate of approximately 22.63% (1362/6039). The most common genotypes identified before the Rota vacation introduction were G1, G2, G3, G12, P [4], P [6], P [8], P [9], and P [10]. Meanwhile, G3 and P [8] genotypes were particularly prevalent after the Rota vaccine introduction. These findings highlight the importance of implementing preventive measures, such as vaccination, to reduce the burden of rotavirus infection in this population. The identified genotypes provide valuable insights for vaccine development and targeted interventions. CONCLUSION: This study contributes to the evidence base for public health interventions and strategies to reduce the impact of rotavirus infection in children under five in Ethiopia. Despite the rollout of the Rota vaccination in Ethiopia, rotavirus heterogeneity is still high, and thus, enhancing vaccination and immunization is essential.


Subject(s)
Diarrhea , Genotype , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Child, Preschool , Humans , Infant , Diarrhea/epidemiology , Diarrhea/prevention & control , Diarrhea/virology , Ethiopia/epidemiology , Prevalence , Rotavirus/classification , Rotavirus/genetics , Rotavirus/immunology , Rotavirus/isolation & purification , Rotavirus Infections/epidemiology , Rotavirus Infections/prevention & control , Rotavirus Infections/virology , Rotavirus Vaccines/administration & dosage , Vaccination/statistics & numerical data
6.
Front Public Health ; 12: 1423573, 2024.
Article in English | MEDLINE | ID: mdl-39175894

ABSTRACT

Background: Rotavirus is globally recognized as an important cause of acute gastroenteritis in young children. Whereas previous studies focused more on sporadic diarrhea, the epidemiological characteristics of rotavirus outbreaks have not been systematically understood. Methods: This systematic review was carried out according to the Preferred Reporting Items for Systematic Review and Meta-Analysis standards, WANFANG, China National Knowledge Infrastructure (CNKI), PubMed, and Web of Science databases were searched from database inception to February 20, 2022. We used SPSS 21.0 statistical software for data analysis, RStudio1.4.1717, and ArcGIS trial version for plotting bar graphs and maps. Results: Among 1,596 articles, 78 were included, with 92 rotavirus outbreaks and 96,128 cases. Most outbreaks (67.39%, 62/92) occurred in winter and spring. The number of rotavirus outbreaks reported in the eastern region was more than that in the western region. Outbreaks were most commonly reported in villages (33/92, 35.87%), followed by hospitals (19, 20.65%). The outbreak duration was longer in factories and workers' living places, and villages, while it was shorter in hospitals. Waterborne transmission was the main transmission mode, with the longest duration and the largest number of cases. Rotavirus groups were identified in 66 outbreaks, with 40 outbreaks (60.61%) caused by Group B rotaviruses and 26 outbreaks (39.39%) caused by Group A rotaviruses. Significant differences were found in duration, number of cases, settings, population distribution, and transmission modes between Groups A and B rotavirus outbreaks. Conclusion: Rotavirus is an important cause of acute gastroenteritis outbreaks in China. It should also be considered in the investigation of acute gastroenteritis outbreaks, especially norovirus-negative outbreaks.


Subject(s)
Disease Outbreaks , Rotavirus Infections , Humans , Rotavirus Infections/epidemiology , Disease Outbreaks/statistics & numerical data , China/epidemiology , Rotavirus , Gastroenteritis/epidemiology , Gastroenteritis/virology , Seasons
7.
J Gen Virol ; 105(8)2024 Aug.
Article in English | MEDLINE | ID: mdl-39163114

ABSTRACT

Equine rotavirus species A (ERVA) G3P[12] and G14P[12] are two dominant genotypes that cause foal diarrhoea with a significant economic impact on the global equine industry. ERVA can also serve as a source of novel (equine-like) rotavirus species A (RVA) reassortants with zoonotic potential as those identified previously in 2013-2019 when equine G3-like RVA was responsible for worldwide outbreaks of severe gastroenteritis and hospitalizations in children. One hurdle to ERVA research is that the standard cell culture system optimized for human rotavirus replication is not efficient for isolating ERVA. Here, using an engineered cell line defective in antiviral innate immunity, we showed that both equine G3P[12] and G14P[12] strains can be rapidly isolated from diarrhoeic foals. The genome sequence analysis revealed that both G3P[12] and G14P[12] strains share the identical genotypic constellation except for VP7 and VP6 segments in which G3P[12] possessed VP7 of genotype G3 and VP6 of genotype I6 and G14P[12] had the combination of VP7 of genotype G14 and VP6 of genotype I2. Further characterization demonstrated that two ERVA genotypes have a limited cross-neutralization. The lack of an in vitro broad cross-protection between both genotypes supported the increased recent diarrhoea outbreaks due to equine G14P[12] in foals born to dams immunized with the inactivated monovalent equine G3P[12] vaccine. Finally, using the structural modelling approach, we provided the genetic basis of the antigenic divergence between ERVA G3P[12] and G14P[12] strains. The results of this study will provide a framework for further investigation of infection biology, pathogenesis and cross-protection of equine rotaviruses.


Subject(s)
Antigens, Viral , Diarrhea , Genotype , Horse Diseases , Rotavirus Infections , Rotavirus , Animals , Horses , Rotavirus/genetics , Rotavirus/immunology , Rotavirus/isolation & purification , Rotavirus/classification , Rotavirus Infections/veterinary , Rotavirus Infections/virology , Rotavirus Infections/immunology , Horse Diseases/virology , Horse Diseases/immunology , Diarrhea/virology , Diarrhea/veterinary , Antigens, Viral/genetics , Antigens, Viral/immunology , Genome, Viral/genetics , Phylogeny , Cell Line
8.
Pediatr Infect Dis J ; 43(9): 902-908, 2024 09 01.
Article in English | MEDLINE | ID: mdl-39163534

ABSTRACT

OBJECTIVE: In June 2022, French health authorities issued a universal recommendation for routine administration and reimbursement of rotavirus vaccines in infants. Given this recent recommendation by French health authorities, we sought to understand the public health impact of a universal rotavirus vaccination strategy compared with no vaccination. MATERIALS AND METHODS: A deterministic, age-structured, nonlinear dynamic transmission model, accounting for herd immunity, was developed. We considered 3 vaccination coverage scenarios: high (95%), medium (75%) and low (55%). Model parameter values were based on published modeling and epidemiological literature. Model outcomes included rotavirus gastroenteritis (RVGE) cases and healthcare resource utilization due to RVGE (hospitalizations, general practitioner or emergency department visits), as well as the number needed to vaccinate to prevent 1 RVGE case (mild or severe) and 1 RVGE-related hospitalization. Model calibration and analyses were conducted using Mathematica 11.3. RESULTS: Over 5 years following implementation, RVGE cases for children under 5 years are estimated to be reduced by 84% under a high vaccination coverage scenario, by 72% under a medium vaccination coverage scenario and by 47% under a low vaccination coverage scenario. Across all scenarios, the number needed to vaccinate to avert 1 RVGE case and hospitalization varied between 1.86-2.04 and 24.15-27.44, respectively. CONCLUSIONS: Rotavirus vaccination with high vaccination coverage in France is expected to substantially reduce the number of RVGE cases and associated healthcare resource utilization.


Subject(s)
Gastroenteritis , Immunization Programs , Public Health , Rotavirus Infections , Rotavirus Vaccines , Humans , Rotavirus Infections/prevention & control , Rotavirus Infections/epidemiology , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/immunology , France/epidemiology , Infant , Child, Preschool , Immunization Programs/statistics & numerical data , Gastroenteritis/prevention & control , Gastroenteritis/virology , Gastroenteritis/epidemiology , Hospitalization/statistics & numerical data , Vaccination/statistics & numerical data , Vaccination Coverage/statistics & numerical data , Rotavirus/immunology , Infant, Newborn , Immunity, Herd
9.
Emerg Infect Dis ; 30(9): 1895-1902, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39174022

ABSTRACT

We assessed the effect of rotavirus vaccination coverage on the number of inpatients with gastroenteritis of all ages in Japan. We identified patients admitted with all-cause gastroenteritis during 2011-2019 using data from the Diagnosis Procedure Combination system in Japan. We used generalized estimating equations with a Poisson distribution, using hospital codes as a cluster variable to estimate the impact of rotavirus vaccination coverage by prefecture on monthly numbers of inpatients with all-cause gastroenteritis. We analyzed 294,108 hospitalizations across 569 hospitals. Higher rotavirus vaccination coverage was associated with reduced gastroenteritis hospitalizations compared with the reference category of vaccination coverage <40% (e.g., for coverage >80%, adjusted incidence rate ratio was 0.87 [95% CI 0.83-0.90]). Our results show that achieving higher rotavirus vaccination coverage among infants could benefit the entire population by reducing overall hospitalizations for gastroenteritis for all age groups.


Subject(s)
Gastroenteritis , Hospitalization , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Vaccination Coverage , Humans , Gastroenteritis/epidemiology , Gastroenteritis/virology , Gastroenteritis/prevention & control , Infant , Japan/epidemiology , Rotavirus Infections/prevention & control , Rotavirus Infections/epidemiology , Rotavirus Vaccines/administration & dosage , Hospitalization/statistics & numerical data , Child, Preschool , Vaccination Coverage/statistics & numerical data , Male , Female , Rotavirus/immunology , Adult , Child , Adolescent , Infant, Newborn , Middle Aged , Young Adult , Aged , Incidence , Vaccination/statistics & numerical data , History, 21st Century
10.
Pan Afr Med J ; 47: 197, 2024.
Article in English | MEDLINE | ID: mdl-39119109

ABSTRACT

Introduction: approximately over 80% of mortalities due to rotavirus occur in countries that have limited resources, especially in sub-Saharan Africa and South Asia. The study was intended to determine the genetic characteristics of rotavirus A in children exhibiting gastroenteritis at Kericho County Referral Hospital. Methods: the study design was cross-sectional. Consecutive sampling was engaged obtaining a sample size of 200 stool samples. Genetic characterization of group A rotavirus strains was done using Enzyme-Linked Immunosorbent Assay. Positive samples underwent Sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Afterwards viewing of the RNA double strands of the rotavirus genome in gels was done using Silver Nitrate. The positive samples underwent RT-PCR amplification followed by sequencing on the pieces of the VP7 or VP4 gene obtained. Results: one hundred and six (53%) samples from males and 94 (47%) from females. Twenty-three samples were positive hence a prevalence of 11.5%. The most affected demographics were children of guardians with secondary school education (51%). The most affected social economic status was housewives (46.5%). The most affected age was 21-30 months at 26.5%. Long electropherotypes were in 22 samples (96%). The G3 genotype of rotavirus A was prevalent 16/23 (69.57%). Conclusion: rotavirus prevalence was 11.5%. The G3 genotype was the most prevalent in circulation. The occurrence of non-typable strains indicated that the strains may be diversified emphasizing the need to include emerging strains within the vaccines in use. Hence the need to continuously monitor the effects in older children.


Subject(s)
Feces , Gastroenteritis , Genotype , Rotavirus Infections , Rotavirus , Humans , Gastroenteritis/virology , Gastroenteritis/epidemiology , Rotavirus/genetics , Rotavirus/isolation & purification , Rotavirus Infections/epidemiology , Rotavirus Infections/virology , Female , Child, Preschool , Cross-Sectional Studies , Male , Infant , Acute Disease , Prevalence , Feces/virology , Kenya/epidemiology , Child , Enzyme-Linked Immunosorbent Assay , Reverse Transcriptase Polymerase Chain Reaction
11.
BMC Vet Res ; 20(1): 305, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982473

ABSTRACT

BACKGROUND: Pigeon Rotavirus A (RVA) infection has been confirmed in pigeons in the last decade as a cause of Young Pigeon Disease (YPD). Although YPD has been known for many years to date, no studies have been conducted to track the spread of RVA infection in pigeons during the racing season. The presented research aims to determine the course of RVA infection during the flights of young racing pigeons in the summer season, in one of the districts in the Mazovian Voivodeship in Poland. RESULTS: Faecal samples of pigeons collected from transport baskets in vehicles transporting pigeons to the starting point were tested. The quantitative RT-PCR (qRT-PCR) was used to detect the genetic material of RVA. Samples taken during 6 flights were analysed. The study showed a percentage increase in infections up to the fourth flight of pigeons, and then their decrease. With Cq values below 20, breeders did not participate in the next flight and/or reported disease in the flock. With positive Cq values of 20 to 30, clinical signs of disease were not reported. Of the 76 breeders participating in the races, at least one positive result was found in 46 (60.5%). Including the occurrence of the disease during the racing season was reported by 11 breeders (14.4%). The main clinical signs in sick pigeons were vomiting, diarrhea and stowed crop. The tested pigeons were not vaccinated against RVA. CONCLUSIONS: During training and racing of pigeons, it is not possible to avoid exposing them to pathogens, including RVA, regardless of whether pigeons from different breeders are placed in the same baskets or are in separate baskets. However, after four flights the number of new cases of the disease decreases which indicates the development of immunity. The qRT-PCR test is useful in the diagnosis and differentiation of clinical (Cq below 20) and subclinical RVA infections in racing pigeons.


Subject(s)
Bird Diseases , Columbidae , Feces , Rotavirus Infections , Rotavirus , Seasons , Animals , Columbidae/virology , Rotavirus Infections/veterinary , Rotavirus Infections/virology , Rotavirus Infections/epidemiology , Bird Diseases/virology , Bird Diseases/epidemiology , Rotavirus/isolation & purification , Feces/virology , Poland/epidemiology
12.
Viruses ; 16(7)2024 Jul 06.
Article in English | MEDLINE | ID: mdl-39066248

ABSTRACT

Rotavirus is infamous for being extremely contagious and for causing diarrhea and vomiting in infants. However, the symptomology is far more complex than what could be expected from a pathogen restricted to the boundaries of the small intestines. Other rotavirus sickness symptoms like fever, fatigue, sleepiness, stress, and loss of appetite have been clinically established for decades but remain poorly studied. A growing body of evidence in recent years has strengthened the idea that the evolutionarily preserved defensive responses that cause rotavirus sickness symptoms are more than just passive consequences of illness and rather likely to be coordinated events from the central nervous system (CNS), with the aim of maximizing the survival of the individual as well as the collective group. In this review, we discuss both established and plausible mechanisms of different rotavirus sickness symptoms as a series of CNS responses coordinated from the brain. We also consider the protective and the harmful nature of these events and highlight the need for further and deeper studies on rotavirus etiology.


Subject(s)
Brain , Rotavirus Infections , Rotavirus , Humans , Rotavirus Infections/virology , Brain/virology , Rotavirus/physiology , Animals , Diarrhea/virology
13.
Viruses ; 16(7)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39066297

ABSTRACT

Rotavirus remains a significant public health threat, especially in low-income countries, where it is the leading cause of severe acute childhood gastroenteritis, contributing to over 128,500 deaths annually. Although the introduction of the Rotarix and RotaTeq vaccines in 2006 marked a milestone in reducing mortality rates, approximately 83,158 preventable deaths persisted, showing ongoing challenges in vaccine accessibility and effectiveness. To address these issues, a novel subcutaneous vaccine formulation targeting multiple rotavirus genotypes has been developed. This vaccine consists of nine VP8* proteins from nine distinct rotavirus genotypes and sub-genotypes (P[4], P[6], P[8]LI, P[8]LIII, P[8]LIV, P[9], P[11], P[14], and P[25]) expressed in E. coli. Two groups of mice were immunized either with a single immunogen, the VP8* from the rotavirus Wa strain (P[8]LI), or with the nonavalent formulation. Preliminary results from mouse immunization studies showed promising outcomes, eliciting antibody responses against six of the nine immunogens. Notably, significantly higher antibody titers against VP8* P[8]LI were observed in the group immunized with the nonavalent vaccine compared to mice specifically immunized against this genotype alone. Overall, the development of parenteral vaccines targeting multiple rotavirus genotypes represents a promising strategy in mitigating the global burden of rotavirus-related morbidity and mortality, offering new avenues for disease prevention and control.


Subject(s)
Antibodies, Viral , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Vaccines, Subunit , Animals , Rotavirus Vaccines/immunology , Rotavirus Vaccines/administration & dosage , Mice , Rotavirus/immunology , Rotavirus/genetics , Vaccines, Subunit/immunology , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/genetics , Rotavirus Infections/prevention & control , Rotavirus Infections/immunology , Rotavirus Infections/virology , Antibodies, Viral/immunology , Antibodies, Viral/blood , Female , Mice, Inbred BALB C , Viral Nonstructural Proteins/immunology , Viral Nonstructural Proteins/genetics , Immunogenicity, Vaccine , Genotype , Capsid Proteins/immunology , Capsid Proteins/genetics , RNA-Binding Proteins/immunology , RNA-Binding Proteins/genetics
14.
Viruses ; 16(7)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39066302

ABSTRACT

Mozambique introduced the Rotarix® vaccine into the National Immunization Program in September 2015. Following vaccine introduction, rotavirus A (RVA) genotypes, G9P[4] and G9P[6], were detected for the first time since rotavirus surveillance programs were implemented in the country. To understand the emergence of these strains, the whole genomes of 47 ELISA RVA positive strains detected between 2015 and 2018 were characterized using an Illumina MiSeq-based sequencing pipeline. Of the 29 G9 strains characterized, 14 exhibited a typical Wa-like genome constellation and 15 a DS-1-like genome constellation. Mostly, the G9P[4] and G9P[6] strains clustered consistently for most of the genome segments, except the G- and P-genotypes. For the G9 genotype, the strains formed three different conserved clades, separated by the P type (P[4], P[6] and P[8]), suggesting different origins for this genotype. Analysis of the VP6-encoding gene revealed that seven G9P[6] strains clustered close to antelope and bovine strains. A rare E6 NSP4 genotype was detected for strain RVA/Human-wt/MOZ/HCN1595/2017/G9P[4] and a genetically distinct lineage IV or OP354-like P[8] was identified for RVA/Human-wt/MOZ/HGJM0644/2015/G9P[8] strain. These results highlight the need for genomic surveillance of RVA strains detected in Mozambique and the importance of following a One Health approach to identify and characterize potential zoonotic strains causing acute gastroenteritis in Mozambican children.


Subject(s)
Genome, Viral , Genotype , Phylogeny , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Vaccines, Attenuated , Rotavirus/genetics , Rotavirus/classification , Rotavirus/isolation & purification , Rotavirus Vaccines/immunology , Rotavirus Vaccines/administration & dosage , Mozambique/epidemiology , Rotavirus Infections/prevention & control , Rotavirus Infections/virology , Rotavirus Infections/epidemiology , Humans , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Whole Genome Sequencing , Animals , Infant , Child, Preschool , Capsid Proteins/genetics , Gastroenteritis/virology , Gastroenteritis/prevention & control , Gastroenteritis/epidemiology , Cattle , Feces/virology
15.
Viruses ; 16(7)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39066309

ABSTRACT

The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently limited as rotaviruses are highly species-specific and replication of human rotaviruses is minimal in mice. To enable characterisation of immune responses to human rotavirus in mice, we have generated chimeric viruses that combat the issue of rotavirus host range restriction. Using reverse genetics, the rotavirus outer capsid proteins (VP4 and VP7) from either human or murine rotavirus strains were encoded in a murine rotavirus backbone. Neonatal mice were infected with chimeric viruses and monitored daily for development of diarrhoea. Stool samples were collected to quantify viral shedding, and antibody responses were comprehensively evaluated. We demonstrated that chimeric rotaviruses were able to efficiently replicate in mice. Moreover, the chimeric rotavirus containing human rotavirus outer capsid proteins elicited a robust antibody response to human rotavirus antigens, whilst the control chimeric murine rotavirus did not. This chimeric human rotavirus therefore provides a new strategy for studying human-rotavirus-specific immunity to the outer capsid, and could be used to investigate factors causing variability in rotavirus vaccine efficacy. This small animal platform therefore has the potential to test the efficacy of new vaccines and antibody-based therapeutics.


Subject(s)
Antibodies, Viral , Capsid Proteins , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Animals , Rotavirus/immunology , Rotavirus/genetics , Mice , Rotavirus Infections/immunology , Rotavirus Infections/prevention & control , Rotavirus Infections/virology , Humans , Antibodies, Viral/immunology , Antibodies, Viral/blood , Capsid Proteins/immunology , Capsid Proteins/genetics , Rotavirus Vaccines/immunology , Rotavirus Vaccines/administration & dosage , Disease Models, Animal , Antigens, Viral/immunology , Antigens, Viral/genetics , Antibody Formation , Virus Shedding , Virus Replication , Feces/virology , Diarrhea/virology , Diarrhea/immunology
16.
Virol J ; 21(1): 160, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039549

ABSTRACT

Porcine Rotavirus (PoRV) is a significant pathogen affecting swine-rearing regions globally, presenting a substantial threat to the economic development of the livestock sector. At present, no specific pharmaceuticals are available for this disease, and treatment options remain exceedingly limited. This study seeks to design a multi-epitope peptide vaccine for PoRV employing bioinformatics approaches to robustly activate T-cell and B-cell immune responses. Two antigenic proteins, VP7 and VP8*, were selected from PoRV, and potential immunogenic T-cell and B-cell epitopes were predicted using immunoinformatic tools. These epitopes were further screened according to non-toxicity, antigenicity, non-allergenicity, and immunogenicity criteria. The selected epitopes were linked with linkers to form a novel multi-epitope vaccine construct, with the PADRE sequence (AKFVAAWTLKAAA) and RS09 peptide attached at the N-terminus of the designed peptide chain to enhance the vaccine's antigenicity. Protein-protein docking of the vaccine constructs with toll-like receptors (TLR3 and TLR4) was conducted using computational methods, with the lowest energy docking results selected as the optimal predictive model. Subsequently, molecular dynamics (MD) simulation methods were employed to assess the stability of the protein vaccine constructs and TLR3 and TLR4 receptors. The results indicated that the vaccine-TLR3 and vaccine-TLR4 docking models remained stable throughout the simulation period. Additionally, the C-IMMSIM tool was utilized to determine the immunogenic triggering capability of the vaccine protein, demonstrating that the constructed vaccine protein could induce both cell-mediated and humoral immune responses, thereby playing a role in eliciting host immune responses. In conclusion, this study successfully constructed a multi-epitope vaccine against PoRV and validated the stability and efficacy of the vaccine through computational analysis. However, as the study is purely computational, experimental evaluation is required to validate the safety and immunogenicity of the newly constructed vaccine protein.


Subject(s)
Antigens, Viral , Computational Biology , Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte , Molecular Dynamics Simulation , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Vaccines, Subunit , Animals , Swine , Rotavirus/immunology , Rotavirus/genetics , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/immunology , Epitopes, B-Lymphocyte/genetics , Rotavirus Vaccines/immunology , Rotavirus Vaccines/chemistry , Rotavirus Vaccines/genetics , Rotavirus Infections/prevention & control , Rotavirus Infections/immunology , Rotavirus Infections/virology , Vaccines, Subunit/immunology , Vaccines, Subunit/genetics , Vaccines, Subunit/chemistry , Antigens, Viral/immunology , Antigens, Viral/genetics , Antigens, Viral/chemistry , Molecular Docking Simulation , Swine Diseases/prevention & control , Swine Diseases/immunology , Swine Diseases/virology , Capsid Proteins/immunology , Capsid Proteins/genetics , Capsid Proteins/chemistry , Vaccine Development , Immunogenicity, Vaccine
17.
Microb Pathog ; 193: 106775, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38960216

ABSTRACT

Rotavirus, a primary contributor to severe cases of infantile gastroenteritis on a global scale, results in significant morbidity and mortality in the under-five population, particularly in middle to low-income countries, including India. WHO-approved live-attenuated vaccines are linked to a heightened susceptibility to intussusception and exhibit low efficacy, primarily attributed to the high genetic diversity of rotavirus, varying over time and across different geographic regions. Herein, molecular data on Indian rotavirus A (RVA) has been reviewed through phylogenetic analysis, revealing G1P[8] to be the prevalent strain of RVA in India. The conserved capsid protein sequences of VP7, VP4 and VP6 were used to examine helper T lymphocyte, cytotoxic T lymphocyte and linear B-cell epitopes. Twenty epitopes were identified after evaluation of factors such as antigenicity, non-allergenicity, non-toxicity, and stability. These epitopes were then interconnected using suitable linkers and an N-terminal beta defensin adjuvant. The in silico designed vaccine exhibited structural stability and interactions with integrins (αvß3 and αIIbß3) and toll-like receptors (TLR2 and TLR4) indicated by docking and normal mode analyses. The immune simulation profile of the designed RVA multiepitope vaccine exhibited its potential to trigger humoral as well as cell-mediated immunity, indicating that it is a promising immunogen. These computational findings indicate potential efficacy of the designed vaccine against rotavirus infection.


Subject(s)
Antigens, Viral , Capsid Proteins , Epitopes, T-Lymphocyte , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Rotavirus/immunology , Rotavirus/genetics , Rotavirus Vaccines/immunology , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/genetics , Rotavirus Infections/prevention & control , Rotavirus Infections/immunology , Capsid Proteins/immunology , Capsid Proteins/genetics , Capsid Proteins/chemistry , Antigens, Viral/immunology , Antigens, Viral/genetics , Humans , India , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Vaccinology/methods , Epitopes, B-Lymphocyte/immunology , Epitopes, B-Lymphocyte/genetics , Phylogeny , Molecular Docking Simulation , Epitopes/immunology , Epitopes/genetics , Vaccine Development
18.
J Infect Dis ; 230(1): e75-e79, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39052701

ABSTRACT

To evaluate how breakthrough rotavirus disease contributes to transmission, we examined the impact of rotavirus vaccination on fecal shedding and duration of illness. We used multivariable linear regression to analyze rotavirus quantity by RT-qPCR and duration among 184 episodes of rotavirus diarrhea positive by ELISA in the PROVIDE study. Vaccinated children had less fecal viral shedding compared to unvaccinated children (mean difference = -0.59 log copies per gram of stool; 95% confidence interval [CI], -.99 to -.19). Duration of illness was on average 0.47 days (95% CI, -.23 to 1.17 days) shorter among vaccinated children. Rotarix vaccination reduces shedding burden among breakthrough cases of rotavirus gastroenteritis. Clinical Trials Registration . NCT01375647.


Subject(s)
Feces , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Vaccines, Attenuated , Virus Shedding , Humans , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/immunology , Rotavirus Infections/prevention & control , Rotavirus Infections/epidemiology , Rotavirus Infections/virology , Infant , Bangladesh/epidemiology , Rotavirus/immunology , Feces/virology , Female , Male , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology , Gastroenteritis/virology , Gastroenteritis/prevention & control , Gastroenteritis/epidemiology , Vaccination , Diarrhea/virology , Diarrhea/prevention & control , Diarrhea/epidemiology , Administration, Oral
19.
J Vet Sci ; 25(4): e55, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39083207

ABSTRACT

IMPORTANCE: Neonatal calf diarrhea is a major cause of mortality in newborn calves worldwide, posing a significant challenge in bovine herds. Group A Bovine Rotaviruses (BRVA) are the primary contributors to severe gastroenteritis in calves under two months old. OBJECTIVES: This study examined the prevalence and molecular characterization of BRVA in neonatal calves in Gujarat, India. METHODS: Sixty-nine diarrheic fecal samples were collected and subjected to various molecular methods of BRVA detection, isolation, and characterization. RESULTS: The latex agglutination test (LAT), electropherotyping (RNA-PAGE), and reverse transcription polymerase chain reaction revealed positivity rates of 39.13%, 20.30%, and 37.70%, respectively. RNA-PAGE identified 11 bands with a 4:2:3:2 migration pattern, indicative of the segmented genome of BRVA. BRVA was successfully isolated from LAT-positive samples, with 26 samples exhibiting clear cytopathic effects upon passage in MA-104 cell lines. Genotyping identified G10 as the predominant G genotype, with P[11] genotypes comprising 76.92% of the isolates. The most common G/P combination was G10P[11], highlighting its zoonotic potential. CONCLUSIONS AND RELEVANCE: These findings underscore the importance of molecular detection and genotyping for effective vaccine development. This study provides crucial insights into the prevalent G and P genotypes of BRVA in Gujarat, India, aiding in the development of targeted control measures.


Subject(s)
Animals, Newborn , Cattle Diseases , Genetic Variation , Genotype , Rotavirus Infections , Rotavirus , Animals , Rotavirus/genetics , Rotavirus/isolation & purification , India/epidemiology , Rotavirus Infections/veterinary , Rotavirus Infections/virology , Rotavirus Infections/epidemiology , Cattle , Cattle Diseases/virology , Cattle Diseases/epidemiology , Animals, Newborn/virology , Prevalence , Feces/virology , Diarrhea/veterinary , Diarrhea/virology , Diarrhea/epidemiology
20.
Zhonghua Er Ke Za Zhi ; 62(7): 643-648, 2024 Jul 02.
Article in Chinese | MEDLINE | ID: mdl-38955682

ABSTRACT

Objective: To investigate the association between intestinal colonization of segmented filamentous bacteria (SFB) and the risk of rotavirus infection, and the possible mechanisms by which SFB resist rotavirus infection. Methods: This case-control study enrolled 50 children aged 0 to 5 years who present to the outpatient Department of Children's Hospital, Zhejiang University School of Medicine with diarrhea and positive stool tests for rotavirus. The children were divided into rotavirus enteritis group and control group consisting of 55 children with non-gastrointestinal and non-infectious surgical diseases.The age and sex composition of the two groups was matched. The DNA of the fecal flora was extracted and SFB was detected by real-time fluorescence quantitative PCR analysis. The children in the rotavirus enteritis group and the control group were subgrouped by age and sex to analyze the differences in SFB positivity rates between different groups, and further compare and analyze the differences in SFB positivity rates between these two groups of children in the ≤2 years old subgroup and the >2-5 years old subgroup. Neutralization test was performed with p3340 protein and rotavirus to determine the relationship between rotavirus infection rate and p3340 concentration in Vero cells. χ2 test or Fisher's exact probability method was used for comparison between the two groups. Results: There were 50 children in the rotavirus enteritis group with an age of (1.7±0.9) years, and 55 children in the control group with an age of (1.8±1.1) years. The positive rate of SFB in children with rotavirus enteritis showed a declining trend across ages groups, with the highest rate of 10/14 in the ≤1 year old group, followed by 67% (14/21) in the >1-2 years old group, 9/15 in the >2-5 years old group, and there was no statistically significant difference (P=0.867). The positive rate of SFB in the control group was 12/15 in the ≤1 year old group, 95% (19/20) in the >1-2 years old group, 50% (10/20) in the >2-5 years old group, with statistical significance (P=0.004). The positive rate of SFB in children with rotavirus enteritis was 74% (20/27) in males and 56% (13/23) in females (χ2=1.71, P=0.192). In the control group, it was 79% (22/28) in males and 70% (19/27) in females (χ2=0.49, P=0.485). The positive rate of SFB was 66% (33/50) in the rotavirus enteritis group and 75% (41/55) in the control group, with no statistically significant (χ2=0.56, P=0.454). In the children ≤2 years old, the SFB positivity rate was 69% (24/35) in the rotavirus enteritis group and 89% (31/35) in the control group, with a statistically significant difference (χ2=4.16, P=0.041). However, in the children >2-5 years old, no statistically significant difference was observed, with the positive rate of SFB being 9/15 in the rotavirus enteritis group and 50% (10/20) in the control group (P=0.734). Pearson correlation analysis revealed a negative correlation between rotavirus infection and SFB positivity (r=-0.87,P<0.001). As the concentration of the p3340 specific protein increased, the luminescence intensity of the luciferase in the Vero cells, which were suitable for cultivating rotavirus, exhibited a decreasing trend (F=4.17, P=0.001). Conclusions: SFB colonization in infants less than 2 years old is associated with a reduced risk of rotavirus infection. Cloning of specific SFB functional protein p3340 neutralizes rotavirus infection of Vero cells, and this mechanism of targeting rotavirus infection differs from the common antiviral mechanism.


Subject(s)
Feces , Rotavirus Infections , Rotavirus , Humans , Infant , Male , Female , Case-Control Studies , Child, Preschool , Feces/virology , Feces/microbiology , Diarrhea/virology , Diarrhea/microbiology , Enteritis/virology , Enteritis/microbiology , Infant, Newborn , Intestines/virology , Intestines/microbiology , Animals
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