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Viruses
Special Issues
Rotavirus and Rotavirus Vaccines
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Rotavirus and Rotavirus Vaccines

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (15 March 2021) | Viewed by 28073

Special Issue Editor

Prof. Dr. Lennart Svensson

E-Mail Website
Guest Editor
Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, 58185 Linköping, Sweden
Interests: viral gastroenteritis; viral pathogenesis/disease mechanisms; human genetics of infectious diseases

Special Issue Information

Dear Colleagues,

Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children under the age of 5. Despite the global introduction of vaccines, infections still result in >200,000 deaths annually, mainly in low-income countries. Infection occurs in mature enterocytes in the small intestine, with reinfections being common throughout life and with reduced severity.

Major gaps in our understanding of rotavirus infection and illness include the pathophysiological mechanisms giving rise to diarrhoea and vomiting, the immune correlates of protection against rotavirus illness, and how rotaviruses interact with the innate immune system. Gaps also includes observations of suboptimal efficacy of current vaccines in certain geographic regions. Recent discoveries suggest that human genetics and microbiota contribute to susceptibility and immunity.

This Special Issue will cover rotavirus vaccines and recent developments in vaccine candidates, rotavirus biology, rotavirus pathogenesis, mechanisms of virus–host cell interactions, and susceptibility.

Prof. Dr. Lennart Svensson
Guest Editor

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Keywords

  • rotavirus
  • gastroenteritis
  • diarrhea
  • vomiting
  • vaccine
  • susceptibility

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Published Papers (7 papers)

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Research

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23 pages, 3070 KiB  
Article
Defining the Recipe for an Optimal Rotavirus Vaccine Introduction in a High-Income Country in Europe
by Baudouin Standaert and Bernd Benninghoff
Viruses 2022, 14(2), 425; https://doi.org/10.3390/v14020425 - 18 Feb 2022
Cited by 2 | Viewed by 1794
Abstract
Observational data over 15 years of rotavirus vaccine introduction in Belgium have indicated that rotavirus hospitalisations in children aged <5 years plateaued at a higher level than expected, and was followed by biennial disease peaks. The research objective was to identify factors influencing [...] Read more.
Observational data over 15 years of rotavirus vaccine introduction in Belgium have indicated that rotavirus hospitalisations in children aged <5 years plateaued at a higher level than expected, and was followed by biennial disease peaks. The research objective was to identify factors influencing these real-world vaccine impact data. We constructed mathematical models simulating rotavirus-related hospitalisations by age group and year for those children. Two periods were defined using different model constructs. First, the vaccine uptake period encompassed the years required to cover the whole at-risk population. Second, the post-uptake period covered the years in which a new infection/disease equilibrium was reached. The models were fitted to the observational data using optimisation programmes with regression and differential equations. Modifying parameter values identified factors affecting the pattern of hospitalisations. Results indicated that starting vaccination well before the peak disease season in the first year and rapidly achieving high coverage was critical in maximising early herd effect and minimising secondary sources of infection. This, in turn, would maximise the reduction in hospitalisations and minimise the size and frequency of subsequent disease peaks. The analysis and results identified key elements to consider for countries initiating an optimal rotavirus vaccine launch programme. Full article
(This article belongs to the Special Issue Rotavirus and Rotavirus Vaccines)
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12 pages, 1511 KiB  
Article
Reduction in Severity of All-Cause Gastroenteritis Requiring Hospitalisation in Children Vaccinated against Rotavirus in Malawi
by Jonathan J. Mandolo, Marc Y. R. Henrion, Chimwemwe Mhango, End Chinyama, Richard Wachepa, Oscar Kanjerwa, Chikondi Malamba-Banda, Isaac T. Shawa, Daniel Hungerford, Arox W. Kamng’ona, Miren Iturriza-Gomara, Nigel A. Cunliffe and Khuzwayo C. Jere
Viruses 2021, 13(12), 2491; https://doi.org/10.3390/v13122491 - 13 Dec 2021
Cited by 3 | Viewed by 3140
Abstract
Rotavirus is the major cause of severe gastroenteritis in children aged <5 years. Introduction of the G1P[8] Rotarix® rotavirus vaccine in Malawi in 2012 has reduced rotavirus-associated hospitalisations and diarrhoeal mortality. However, the impact of rotavirus vaccine on the severity of gastroenteritis [...] Read more.
Rotavirus is the major cause of severe gastroenteritis in children aged <5 years. Introduction of the G1P[8] Rotarix® rotavirus vaccine in Malawi in 2012 has reduced rotavirus-associated hospitalisations and diarrhoeal mortality. However, the impact of rotavirus vaccine on the severity of gastroenteritis presented in children requiring hospitalisation remains unknown. We conducted a hospital-based surveillance study to assess the impact of Rotarix® vaccination on the severity of gastroenteritis presented by Malawian children. Stool samples were collected from children aged <5 years who required hospitalisation with acute gastroenteritis from December 2011 to October 2019. Gastroenteritis severity was determined using Ruuska and Vesikari scores. Rotavirus was detected using enzyme immunoassay. Rotavirus genotypes were determined using nested RT-PCR. Associations between Rotarix® vaccination and gastroenteritis severity were investigated using adjusted linear regression. In total, 3159 children were enrolled. After adjusting for mid-upper arm circumference (MUAC), age, gender and receipt of other vaccines, all-cause gastroenteritis severity scores were 2.21 units lower (p < 0.001) among Rotarix®-vaccinated (n = 2224) compared to Rotarix®-unvaccinated children (n = 935). The reduction in severity score was observed against every rotavirus genotype, although the magnitude was smaller among those infected with G12P[6] compared to the remaining genotypes (p = 0.011). Each one-year increment in age was associated with a decrease of 0.43 severity score (p < 0.001). Our findings provide additional evidence on the impact of Rotarix® in Malawi, lending further support to Malawi’s Rotarix® programme. Full article
(This article belongs to the Special Issue Rotavirus and Rotavirus Vaccines)
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16 pages, 4546 KiB  
Article
Rescue of Infectious Rotavirus Reassortants by a Reverse Genetics System Is Restricted by the Receptor-Binding Region of VP4
by Alexander Falkenhagen, Marno Huyzers, Alberdina A. van Dijk and Reimar Johne
Viruses 2021, 13(3), 363; https://doi.org/10.3390/v13030363 - 25 Feb 2021
Cited by 8 | Viewed by 2677
Abstract
The rotavirus species A (RVA) capsid contains the spike protein VP4, which interacts with VP6 and VP7 and is involved in cellular receptor binding. The capsid encloses the genome consisting of eleven dsRNA segments. Reassortment events can result in novel strains with changed [...] Read more.
The rotavirus species A (RVA) capsid contains the spike protein VP4, which interacts with VP6 and VP7 and is involved in cellular receptor binding. The capsid encloses the genome consisting of eleven dsRNA segments. Reassortment events can result in novel strains with changed properties. Using a plasmid-based reverse genetics system based on simian RVA strain SA11, we previously showed that the rescue of viable reassortants containing a heterologous VP4-encoding genome segment was strain-dependent. In order to unravel the reasons for the reassortment restrictions, we designed here a series of plasmids encoding chimeric VP4s. Exchange of the VP4 domains interacting with VP6 and VP7 was not sufficient for rescue of viable viruses. In contrast, the exchange of fragments encoding the receptor-binding region of VP4 resulted in virus rescue. All parent strains and the rescued reassortants replicated efficiently in MA-104 cells used for virus propagation. In contrast, replication in BSR T7/5 cells used for plasmid transfection was only efficient for the SA11 strain, whereas the rescued reassortants replicated slowly, and the parent strains failing to produce reassortants did not replicate. While future research in this area is necessary, replication in BSR T7/5 cells may be one factor that affects the rescue of RVAs. Full article
(This article belongs to the Special Issue Rotavirus and Rotavirus Vaccines)
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Review

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22 pages, 3354 KiB  
Review
Prevalence, Pattern and Genetic Diversity of Rotaviruses among Children under 5 Years of Age with Acute Gastroenteritis in South Africa: A Systematic Review and Meta-Analysis
by Cornelius A. Omatola, Ropo E. Ogunsakin and Ademola O. Olaniran
Viruses 2021, 13(10), 1905; https://doi.org/10.3390/v13101905 - 23 Sep 2021
Cited by 16 | Viewed by 4239
Abstract
Rotavirus is the most significant cause of severe acute gastroenteritis among children under 5 years of age, worldwide. Sub-Saharan Africa particularly bears the brunt of the diarrheal deaths. A meta-analysis was conducted on 43 eligible studies published between 1982 and 2020 to estimate [...] Read more.
Rotavirus is the most significant cause of severe acute gastroenteritis among children under 5 years of age, worldwide. Sub-Saharan Africa particularly bears the brunt of the diarrheal deaths. A meta-analysis was conducted on 43 eligible studies published between 1982 and 2020 to estimate the pooled prevalence of rotavirus infection and changes in the main rotavirus strains circulating before and after vaccine introduction among under-five children in South Africa. The pooled national prevalence of rotavirus infection was estimated at 24% (95% CI: 21–27%) for the pre-vaccination period and decreased to 23% (95% CI: 21–25%) in the post-vaccination period. However, an increased number of cases was observed in the KwaZulu-Natal (21–28%) and Western Cape (18–24%) regions post-vaccination. The most dominant genotype combinations in the pre-vaccine era was G1P[8], followed by G2P[4], G3P[8], and G1P[6]. After vaccine introduction, a greater genotype diversity was observed, with G9P[8] emerging as the predominant genotype combination, followed by G2P[4], G12P[8], and G1P[8]. The introduction of the rotavirus vaccine was associated with a reduction in the burden of rotavirus-associated diarrhea in South Africa, although not without regional fluctuation. The observed changing patterns of genotype distribution highlights the need for ongoing surveillance to monitor the disease trend and to identify any potential effects associated with the dynamics of genotype changes on vaccine pressure/failure. Full article
(This article belongs to the Special Issue Rotavirus and Rotavirus Vaccines)
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11 pages, 2503 KiB  
Review
Viroplasms: Assembly and Functions of Rotavirus Replication Factories
by Guido Papa, Alexander Borodavka and Ulrich Desselberger
Viruses 2021, 13(7), 1349; https://doi.org/10.3390/v13071349 - 12 Jul 2021
Cited by 46 | Viewed by 8277
Abstract
Viroplasms are cytoplasmic, membraneless structures assembled in rotavirus (RV)-infected cells, which are intricately involved in viral replication. Two virus-encoded, non-structural proteins, NSP2 and NSP5, are the main drivers of viroplasm formation. The structures (as far as is known) and functions of these proteins [...] Read more.
Viroplasms are cytoplasmic, membraneless structures assembled in rotavirus (RV)-infected cells, which are intricately involved in viral replication. Two virus-encoded, non-structural proteins, NSP2 and NSP5, are the main drivers of viroplasm formation. The structures (as far as is known) and functions of these proteins are described. Recent studies using plasmid-only-based reverse genetics have significantly contributed to elucidation of the crucial roles of these proteins in RV replication. Thus, it has been recognized that viroplasms resemble liquid-like protein–RNA condensates that may be formed via liquid–liquid phase separation (LLPS) of NSP2 and NSP5 at the early stages of infection. Interactions between the RNA chaperone NSP2 and the multivalent, intrinsically disordered protein NSP5 result in their condensation (protein droplet formation), which plays a central role in viroplasm assembly. These droplets may provide a unique molecular environment for the establishment of inter-molecular contacts between the RV (+)ssRNA transcripts, followed by their assortment and equimolar packaging. Future efforts to improve our understanding of RV replication and genome assortment in viroplasms should focus on their complex molecular composition, which changes dynamically throughout the RV replication cycle, to support distinct stages of virion assembly. Full article
(This article belongs to the Special Issue Rotavirus and Rotavirus Vaccines)
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11 pages, 540 KiB  
Review
Effect of Infant and Maternal Secretor Status on Rotavirus Vaccine Take—An Overview
by Sumit Sharma and Johan Nordgren
Viruses 2021, 13(6), 1144; https://doi.org/10.3390/v13061144 - 14 Jun 2021
Cited by 7 | Viewed by 2779
Abstract
Histo-blood group antigens, which are present on gut epithelial surfaces, function as receptors or attachment factors and mediate susceptibility to rotavirus infection. The major determinant for susceptibility is a functional FUT2 enzyme which mediates the presence of α-1,2 fucosylated blood group antigens in [...] Read more.
Histo-blood group antigens, which are present on gut epithelial surfaces, function as receptors or attachment factors and mediate susceptibility to rotavirus infection. The major determinant for susceptibility is a functional FUT2 enzyme which mediates the presence of α-1,2 fucosylated blood group antigens in mucosa and secretions, yielding the secretor-positive phenotype. Secretors are more susceptible to infection with predominant rotavirus genotypes, as well as to the commonly used live rotavirus vaccines. Difference in susceptibility to the vaccines is one proposed factor for the varying degree of efficacy observed between countries. Besides infection susceptibility, secretor status has been found to modulate rotavirus specific antibody levels in adults, as well as composition of breastmilk in mothers and microbiota of the infant, which are other proposed factors affecting rotavirus vaccine take. Here, the known and possible effects of secretor status in both infant and mother on rotavirus vaccine take are reviewed and discussed. Full article
(This article belongs to the Special Issue Rotavirus and Rotavirus Vaccines)
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9 pages, 639 KiB  
Review
Understanding the Central Nervous System Symptoms of Rotavirus: A Qualitative Review
by Arash Hellysaz and Marie Hagbom
Viruses 2021, 13(4), 658; https://doi.org/10.3390/v13040658 - 11 Apr 2021
Cited by 14 | Viewed by 4161
Abstract
This qualitative review on rotavirus infection and its complications in the central nervous system (CNS) aims to understand the gut–brain mechanisms that give rise to CNS driven symptoms such as vomiting, fever, feelings of sickness, convulsions, encephalitis, and encephalopathy. There is substantial evidence [...] Read more.
This qualitative review on rotavirus infection and its complications in the central nervous system (CNS) aims to understand the gut–brain mechanisms that give rise to CNS driven symptoms such as vomiting, fever, feelings of sickness, convulsions, encephalitis, and encephalopathy. There is substantial evidence to indicate the involvement of the gut–brain axis in symptoms such as vomiting and diarrhea. The underlying mechanisms are, however, not rotavirus specific, they represent evolutionarily conserved survival mechanisms for protection against pathogen entry and invasion. The reviewed studies show that rotavirus can exert effects on the CNS trough nervous gut–brain communication, via the release of mediators, such as the rotavirus enterotoxin NSP4, which stimulates neighboring enterochromaffin cells in the intestine to release serotonin and activate both enteric neurons and vagal afferents to the brain. Another route to CNS effects is presented through systemic spread via lymphatic pathways, and there are indications that rotavirus RNA can, in some cases where the blood brain barrier is weakened, enter the brain and have direct CNS effects. CNS effects can also be induced indirectly as a consequence of systemic elevation of toxins, cytokines, and/or other messenger molecules. Nevertheless, there is still no definitive or consistent evidence for the underlying mechanisms of rotavirus-induced CNS complications and more in-depth studies are required in the future. Full article
(This article belongs to the Special Issue Rotavirus and Rotavirus Vaccines)
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