Driving forces of continuing evolution of rotaviruses

Rotaviruses are non-enveloped double-stranded RNA virus that causes acute diarrheal diseases in children(<5 years).More than 90%of the global rotavirus infection in humans was caused by Rotavirus group A.Rotavirus infection has caused more than 200000 deaths annually and predominantly occurs in the low-income countries.Rotavirus evolution is indicated by the strain dynamics or the emergence of the unprecedented strain.The major factors that drive the rotavirus evolution include the genetic shift that is caused by the reassortment mechanism,either in the intra-or the inter-genogroup.However,other factors are also known to have an impact on rotavirus evolution.This review discusses the structure and types,epidemiology,and evolution of rotaviruses.This article also reviews other supplemental factors of rotavirus evolution,such as genetic reassortment,mutation rate,glycan specificity,vaccine introduction,the host immune respo-nses,and antiviral drugs.

Genotype analysis of rotaviruses isolated from children during a phase III clinical trial with the hexavalent rotavirus vaccine in China

The oral hexavalent live human-bovine reassortant rotavirus vaccine(RV6)developed by Wuhan Institute of Biological Products Co.,Ltd(WIBP)has finished a randomized,placebo-controlled phase III clinical trial in four provinces of China in 2021.The trail demonstrated that RV6 has a high vaccine efficacy against the prevalent strains and is safe for use in infants.During the phase III clinical trial(2019–2021),200 rotavirus-positive fecal samples from children with RV gastroenteritis(RVGE)were further studied.Using reverse transcription-polymerase chain reaction and high-throughput sequencing,VP7 and VP4 sequences were obtained and their genetic characteristics,as well as the differences in antigenic epitopes of VP7,were analyzed in detail.Seven rotavirus genotypes were identified.The predominant rotavirus genotype was G9P[8](77.0%),followed by prevalent strains G8P[8](8.0%),G3P[8](3.5%),G3P[9](1.5%),G1P[8](1.0%),G2P[4](1.0%),and G4P[6](1.0%).The amino acid sequence identities of G1,G2,G3,G4,G8,and G9 genotypes of isolates compared to the vaccine strains were 98.8%,98.2%–99.7%,88.4%–99.4%,98.2%,94.2%–100%,and 93.9%–100%,respectively.Notably,the vaccine strains exhibited high similarity in amino acid sequence,with only minor differences in antigenic epitopes compared to the Chinese endemic strains.This supports the potential application of the vaccine in preventing diseases caused by rotaviruses.

Evaluation of the infectivity,gene and antigenicity persistence of rotaviruses by free chlorine disinfection

The effects of free chlorine disinfection of tap water and wastewater effluents on the infectivity, gene integrity and surface antigens of rotaviruses were evaluated by a bench-scale chlorine disinfection experiments. Plaque assays, integrated cell culture-quantitative RT- PCR （ICC-RT-qPCR）, RT-qPCR, and enzyme-linked immunosorbent assays （ELISA）, respectively, were used to assess the influence of the disinfectant on virus infectivity as well as genetic and antigenic integrity of simian rotavirus SA11 as a surrogate for human rotaviruses. The ICC-RT-qPCR was able to detect rotaviruses survival from chlorine disinfection at chlorine dose up to 20 mg/L （60 min contact）, which suggested a required chlorine dose of 5 folds （from 1 to 5 mg/L） higher than that indicated by the plaque assay to achieve 1.8 log10 reductions in tap water with 60 rain exposing. The VP7 gene was more resistant than the infectivity and existed at chlorine dose up to 20 mg/L （60 min contact）, while the antigencity was undetectable with chlorine dose more than 5 mg/L （60 min contact）. The water quality also impacted the inactivation efficiencies, and rotaviruses have a relatively higher resistant in secondary effluents than in the tap water under the same chlorine disinfection treatments. This study indicated that rotaviruses have a higher infectivity, gene and antigencity resistance to chlorine than that previously indicated by plaque assay only, which seemed to underestimate the resistance of rotaviruses to chlorine and the risk of rotaviruses in environments. Present results also suggested that re-evaluation of resistance of other waterborne viruses after disinfections by more sensitive infectivity detection method （such as ICC-RT-qPCR） may be necessary, to determine the adequate disinfectant doses required for the inactivation of waterborne viruses.

The protective role of prebiotics and probiotics on diarrhea and gut damage in the rotavirus-infected piglets

Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to treat the disease, and the related vaccines have no obvious efficiency in some countries. Via analyzing the pathogenesis of rotavirus, it inducing diarrhea is mainly due to disturb enteric nervous system, destroy gut mucosal integrity, induce intracellular electrolyte imbalance, and impair gut microbiota and immunity. Many studies have already proved that prebiotics and probiotics can mitigate the damage and diarrhea induced by rotavirus infection in hosts. Based on these, the current review summarizes and discusses the effects and mechanisms of prebiotics and probiotics on rotavirus-induced diarrhea in piglets. This information will highlight the basis for the swine production utilization of prebiotics and probiotics in the prevention or treatment of rotavirus infection in the future.

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, China in 2019

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China.Methods This study included individuals aged 28 days–85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA.Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0–1 year,and RVA is the key pathogen circulating in patients 6–10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains.Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Rotavirus, Norovirus and Astrovirus in Children Aged 0 - 5 Years: Evolution of Prevalence over 10 Years (2013-2023) Following the Introduction of Rotavirus Vaccines in Burkina Faso

Rotaviruses, noroviruses, and astroviruses are responsible for gastroenteritis in children under 5 years old. The objective of our study was to estimate the evolution of prevalence of rotavirus, norovirus and astrovirus infections in children aged 0 to 5 years with gastroenteritis, after the introduction of rotavirus vaccines in Burkina Faso. This cross-sectional study was conducted between January and December 2023, collecting 100 stool samples from children with gastroenteritis at Saint Camille Hospital in Ouagadougou and the Charles De Gaulle University Paediatric Hospital. Noroviruses and astroviruses were detected using multiplex real-time PCR with a Sacace biotechnology detection kit. Data analysis was performed with Stata statistical software, version 16.0. The prevalence of norovirus infections was 14% and astrovirus infections were 9%. Rotavirus infections were found at prevalence of 15%. The age group most affected by norovirus and astrovirus infections was 0 - 12 months, with respective prevalence rates of 73.34% and 55.56%. The most frequently observed clinical signs in children infected with astrovirus were fever (77.78%), diarrhea (55.56%), and vomiting (44.44%). The introduction of rotavirus vaccines has reduced rotavirus-related infections. However, this has not significantly impacted the prevalence of norovirus and astrovirus infections in Burkina Faso.

Exploring the impact of rotavirus vaccination on antibiotic prescription and resistance:A comprehensive systematic review

BACKGROUND Rotavirus is a highly contagious virus responsible for a significant burden of acute gastroenteritis,particularly among infants and young children worldwide,however,vaccination against this viral agent is available.Several studies have hypothesized that rotavirus vaccination has been linked to lower rates of antibiotic resistance.AIM To assess the relationship between rotavirus vaccination and antibiotic resistance.METHODS The present systematic review was tailored based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.Several electronic databases(PubMed/MEDLINE,Scopus and Web of Science)were searched independently by two investigators in order to retrieve relevant publications published until April 2023 that investigated the aforementioned research question.RESULTS The comprehensive database search identified a total of 91 records.After the duplicates were removed(n=75),we screened the titles and abstracts of 16 potentially eligible publications.After the irrelevant records were excluded(n=5),we screened the full texts of 11 manuscripts.Finally,5 studies were entered into the qualitative and quantitative analysis.CONCLUSION In conclusion,all the studies support the idea that vaccinations can reduce the need for antibiotic prescriptions which could potentially contribute to mitigating antibiotic resistance.However,to fully comprehend the mechanisms of antibiotic resistance,enhance treatment guidelines,and consider diverse demographic situations,further research is necessary to use evidence-based strategies to fight antibiotic misuse and resistance.

Frequency of Rotavirus among under 5 Children Admitted to Wad Madani Pediatric Teaching Hospital with Diarrhea, Gezira State, Sudan (2021-2022)

Rotavirus is the leading cause of acute gastroenteritis and responsible for 20% of death in children under 5 years of age approximately 111 million episodes of gastroenteritis due to Rotavirus in under 5 children, which result in 25 million visits to clinic, 2 million hospitalization and 352,000 - 592,000 deaths. Children in the poorest countries account 82% of rotaviruses death. Diarrhea disease are major cause of death and disease among children under five years, a child on average suffers 2 to 3 attacks of diarrhea every year. Stools samples were collected from 196 children suffering from diarrhea and were tested for rotaviruses by immune chromatography test antigen (ICT-Ag), ELISA and RT PCR The data were analyzed using statistical package for the Social Sciences (SPSS). The results showed that prevalence of rotavirus was 26/196 (13.3%) by ICT Ag and ELISA and confirmed by RT-PC R. 87.8% of the children were vaccinated by Rota vaccine, 70% of their mothers not using soap for cleaning the children and thought diarrhea not infectious disease and believed it was caused by teething. In conclusion there was a decrease in prevalence of diarrhea by Rotavirus due to insertion of Rota vaccine in routine vaccination, rotavirus infection mostly occurs in poor family that not able to provide safe water and due to poor sanitation and low education of mother beside that some children suffered from malnutrition, so it recommended to incorporate ELISA as a diagnostic tool in routine diagnosis of rotavirus among children suffered from gastroenteritis.

Molecular detection of viruses in Kenyan bats and discovery of novel astroviruses, caliciviruses and rotaviruses

This is the first country-wide surveillance of bat-borne viruses in Kenya spanning from 2012-2015 covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of Kenyan bats. We screened for both DNA and RNA viruses; specifically, astroviruses （AstVs）, adenoviruses （ADVs）, caliciviruses （CalVs）, coronaviruses （CoVs）, flaviviruses, filoviruses, paramyxoviruses （PMVs）, polyomaviruses （PYVs） and rotaviruses. We used family-specific primers, amplicon sequencing and further characterization by phyloge- netic analysis. Except for filoviruses, eight virus families were detected with varying distributions and positive rates across the five regions （former provinces） studied. AstVs （12.83%）, CoVs （3.97%）, PMV （2.4%）, ADV （2.26%）, PYV （1.65%）, CalVs （0.29%）, rotavirus （0.19%） and flavivirus （0.19%）. Novel CalVs were detected in Rousettus aegyptiacus and Mops condylurus while novel Rotavirus-A-related viruses were detected in Taphozous bats and R. aegyptiacus. The two Rotavirus A （RVA） strains detected were highly related to human strains with VP6 genotypes 12 and 116. Genotype 116 has previously been assigned to human RVA-strain B10 from Kenya only, which raises public health concern, particularly considering increased human-bat interaction. Additionally, 229E-like bat CoVs were detected in samples originating from Hipposideros bats roosting in sites with high human activity. Our findings confirm the presence of diverse viruses in Kenyan bats while providing extended knowledge on bat virus distribution. The detection of viruses highly related to human strains and hence of public health concern, underscores the importance of continuous surveillance.

Clinical factors predicting rotavirus diarrhea in children:A crosssectional study from two hospitals

BACKGROUND Rotavirus is still a significant contributing morbidity and mortality in pediatric patients.AIM To look at clinical signs and symptoms and laboratory findings that can predict rotavirus gastroenteritis compared to non-rotavirus gastroenteritis.METHODS This was a cross-sectional study with medical records obtained from December 2015 to December 2019.Inclusion criteria for this study include all hospitalised pediatric patients(0-18 years old)diagnosed with suspected rotavirus diarrhea.The receiver operating curve and Hosmer-Lemeshow test would be used to assess the final prediction findings'calibration(goodness of fit)and discrimination performance.RESULTS This study included 267 participants with 187(70%)rotavirus-diarrhea cases.The patients were primarily male in both rotavirus(65.2%)and non-rotavirus(62.5%)groups.The median age is 1.33 years old(0.08-17.67 years old).Multivariate analysis shows that wet season(OR_(adj)=2.5;95%CI:1.3-4.8,Padj=0.006),length of stay(LOS)≥3 days(OR_(adj)=5.1;95%CI:1.4-4.8,Padj=0.015),presence of abdominal pain(OR_(adj)=3.0;95%CI:1.3-6.8,Padj=0.007),severe dehydration(OR_(adj)=2.9;95%CI:1.1-7.9,Padj=0.034),abnormal white blood cell counts(OR_(adj)=2.8;95%CI:1.3-6.0,Padj=0.006),abnormal random blood glucose(OR_(adj)=2.3;95%CI:1.2-4.4,Padj=0.018)and presence of fecal leukocytes(OR_(adj)=4.1,95%CI:1.7-9.5,Padj=0.001)are predictors of rotavirus diarrhea.The area under the curve for this model is 0.819(95%CI:0.746-0.878,P value<0.001),which shows that this model has good discrimination.CONCLUSION Wet season,LOS≥3 d,presence of abdominal pain,severe dehydration,abnormal white blood cell counts,abnormal random blood glucose,and presence of fecal leukocytes predict rotavirus diarrhea.

Gastrointestinal tract and viral pathogens

Viral gastroenteritis is the most common viral illness that affects the gastro-intestinal(GI)tract,causing inflammation and irritation of the lining of the stomach and intestines.Common signs and symptoms associated with this condition include abdominal pain,diarrhea,and dehydration.The infections commonly involved in viral gastroenteritis are rotavirus,norovirus,and adenovirus,which spread through the fecal-oral and contact routes and cause non-bloody diarrhea.These infections can affect both immunocompetent and immunocompromised individuals.Since the pandemic in 2019,coronavirus gastroenteritis has increased in incidence and prevalence.Morbidity and mortality rates from viral gastroenteritis have declined significantly over the years due to early recognition,treatment with oral rehydration salts,and prompt vaccination.Improved sanitation measures have also played a key role in reducing the transmission of infection.In addition to viral hepatitis causing liver disease,herpes virus,and cytomegalovirus are responsible for ulcerative GI disease.They are associated with bloody diarrhea and commonly occur in im-munocompromised individuals.Hepatitis viruses,Epstein-Barr virus,herpesvirus 8,and human papillomavirus have been involved in benign and malignant diseases.This mini review aims to list different viruses affecting the GI tract.It will cover common symptoms aiding in diagnosis and various important aspects of each viral infection that can aid diagnosis and management.This will help primary care physicians and hospitalists diagnose and treat patients more easily.

Neonatal erythema multiforme associated with a rotavirus infection:A case report

BACKGROUND Erythema multiforme(EM)is an extremely rare condition in neonates,and studies suggest its association with certain infections and neonatal vaccinations;however,few specific etiological agents have been identified.Rotavirus,a common pathogenic gastrointestinal virus in the neonatal period that is preventable via vaccination,has not been identified as a possible etiology.We report the case of a neonate who was referred for skin lesions presenting as EM,where a meticulous workup identified rotavirus as the sole causative agent.CASE SUMMARY A 14-day-old male infant was admitted to our hospital with a 1-day history of skin lesions.No medical history or medication intake was recorded.Except for the complaint of skin lesions,the caregivers denied any abnormal symptoms.Multiple tests,including routine laboratory evaluations,were performed to identify the cause of skin lesions.Serological tests for Immunoglobulin M for Toxoplasma,Rubella,Cytomegalovirus,Herpes Simplex Virus,and Epstein-Barr virus viral-capsid antigen were all negative.Multiple polymerase chain reaction(PCR)tests for respiratory viruses and bacterial pathogens were negative(including the severe acute respiratory syndrome coronavirus 2).Multiple PCR tests for gastrointestinal viruses and bacterial pathogens demonstrated evidence of rotavirus infection.No growth was reported in the blood and urine cultures.The patient received intravenous fluids for hydration;meanwhile,no other medications were prescribed.The lesions improved rapidly without specific treatment,and full recovery was achieved within a week.CONCLUSION The possibility of rotavirus,a major cause of pediatric gastrointestinal infections,being a trigger for neonatal EM should be considered.

树突状细胞与轮状病毒相互作用机制研究进展

轮状病毒（Rotavirus,RV）属于呼肠孤病毒科轮状病毒属成员,是引起婴幼儿和其他幼龄动物腹泻的主要病原之一,全世界每年约有400 000名儿童因感染此病毒而死亡（[1]）。RV感染已成为全球性的健康问题,

Inflammatory and oxidative stress in rotavirus infection

Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum(ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species(ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virusassociated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines.

轮状病毒疫苗研究进展

轮状病毒（Rotavirus,RV）是引起多种幼龄动物以及婴幼儿腹泻的重要病原体。轮状病毒最早是Mebus在1969年从犊牛粪便中发现的,1973年澳大利亚科学家Bishop等在患有严重腹泻婴儿的十二指肠黏膜及粪便中发现了一种新的病毒粒子。在非洲和亚洲的撒哈拉以南地区,据调查超过三分之一的婴幼儿腹泻及胃肠炎疾病由轮状病毒引起,每年导致50万-60万婴幼儿死亡。

小鼠轮状病毒感染

轮状病毒(Rotavirus)是各种幼龄动物非菌性腹泻的主要病原之一。小鼠的流行性腹泻就是由于它所引起的。此外,人、绵羊、山羊、羚羊、幼驹、鹿、犊牛、兔、猴、猪、犬、鸡、火鸡,鸭等都有很多关于发生轮状病毒感染的报道。也曾在棕熊、豚鼠检测到特异性抗病毒抗体。小鼠轮状病毒在鼠群中感染很普遍,特别是在第一胎仔鼠中,且死亡率高,给生产带来很大的损失。此病易与由其它病毒和细菌引起的腹泻相混淆。现就它的一些特性做一概述。一、形态、理化学特性及分类: 1947年Cheever等人第一次对小鼠流行性腹泻(EDIM)做了报道。电镜检查可以观察到两种形态的病毒颗粒:一种是有外衣壳的完整病毒粒子,直径为75—80nm,一般只有在用回肠做直接印片时才能观察到;

河南省人轮状病毒核酸区带电泳分析研究

轮状病毒(RV)是世界范围内儿童、特别是6月—2岁婴幼儿腹泻的重要病因。近年来发现它同样是成人腹泻的主要病因之一。按其血清学特征,已发现了四个血清群人轮状病毒(HRV),但进行不同血清群 RV 肠炎流行病学调查。

乳鼠流行性腹泻研究概况

乳鼠流行性腹泻(EDIM)是开放饲养小鼠的乳鼠常见疾病,早在1947年,Cheever等首次系统地研究了实验乳鼠所发生的流行性腹泻。其特点为2周龄乳鼠发生急性腹泻,患病率高,传染性强,但死亡率相对较低。1957年Kraft认为本病致病原是病毒。1963年又经Adams用电镜观察证实,起名为乳鼠流行性腹泻病毒。病毒形态与引起牛、猴、猪和羊等腹泻的轮状病毒(Rotavirus,RV)相似,以后证明它与这些RV有血清学关系,定名为小鼠轮状病毒(MRV)。由于其基因组由双股RNA组成,归为呼肠孤病毒科,轮状病毒属。最近,有资料表明,我国也有许多品系乳鼠发生由MRV引起的EDIM。一、病原学MRV形态为典型RV。完整MRV直径75—80nm,缺乏外膜的不完整MRV直径约为65nm左右。它在56℃或60℃半小时内仍具感染性。

Involvement of aquaporins in a mouse model of rotavirus diarrhea

Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems to occur because of aquaporins(AQPs). Accumulating evidence indicates that alterations in AQPs may play an important role in pathogenesis. Here, we focus on changes in AQPs in a mouse model of rotavirus diarrhea. In the present study, 32 of 35 mice developed diarrhea and mild dehydration within 24 hours after infection with rotavirus strain SA11. Intestinal epithelial cells demonstrated cytoplasmic vacuolation, malaligned villi, and atrophy. AQP1 expression was significantly attenuated in the ileum and colon in comparison with controls; likewise, AQP4 and-8 protein expression were significantly decreased in the colon of rotavirus diarrhea-infected mice. In contrast, AQP3 protein expression was significantly increased in the colon of rotavirus-infected mice in comparison with controls. These results indicate that rotavirus diarrhea is associated with the downregulation of AQP1,-4, and-8 expression. Therefore, AQPs play an important role in rotavirus diarrhea.

Prevalence and Genotypes of Rotavirus A and Human Adenovirus among Hospitalized Children with Acute Gastroenteritis in Fujian, China, 2009-2017

Gastroenteritis is an infectious diarrhea that has been considered as an important cause of hospitalizations and death in children aged < 5 years, particularly in developing countries. Unsanitary water, contaminated food, poor hygiene, and inadequate disposal of waste and feces are all risk factors for gastroenteritis, resulting in the higher incidence in developing countries. Gastroenteritis is generally caused by viral infections, among which rotavirus (RV) infections have been reported to be the most common, especially among young children aged < 5 years with acute gastroenteritis in Asia and Africa[1]. Other viruses associated with acute gastroenteritis include human Adenovirus (HAdV), Norovirus, Sapovirus (SaV), human Astrovirus (HAstV), and Aichi virus. Recent research has reported that adenovirus types 40 and 41, belonging to species F, cause gastroenteritis and were therefore termed as enteric adenoviruses. In addition, non-enteric HAdV species such as A, B, C, and D have been associated with diarrheal.