scholarly journals Antigenic Diversity of Human Norovirus Capsid Proteins Based on the Cross-Reactivities of Their Antisera

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 986
Author(s):  
Junshan Gao ◽  
Yueting Zuo ◽  
Liang Xue ◽  
Linping Wang ◽  
Yanhui Liang ◽  
...  

Human norovirus (HuNoV), which is the major causative agent of acute gastroenteritis, has broad antigenic diversity; thus, the development of a broad-spectrum vaccine is challenging. To establish the relationship between viral genetic diversity and antigenic diversity, capsid P proteins and antisera of seven GI and 16 GII HuNoV genotypes were analyzed. Enzyme-linked immunosorbent assays showed that HuNoV antisera strongly reacted with the homologous capsid P proteins (with titers > 5 × 104). However, 17 (73.9%) antisera had weak or no cross-reactivity with heterologous genotypes. Interestingly, the GII.5 antiserum cross-reacted with seven (30.4%) capsid P proteins (including pandemic genotypes GII.4 and GII.17), indicating its potential use for HuNoV vaccine development. Moreover, GI.2 and GI.6 antigens reacted widely with heterologous antisera (n ≥ 5). Sequence alignment and phylogenetic analyses of the P proteins revealed conserved regions, which may be responsible for the immune crossover reactivity observed. These findings may be helpful in identifying broad-spectrum epitopes with clinical value for the development of a future vaccine.

2020 ◽  
Author(s):  
Noah Avery Schuster

An initial outbreak of coronavirus disease 2019 (COVID-19) in China has resulted in a massive global pandemic causing well over 16,500,000 cases and 650,000 deaths worldwide. The virus responsible, SARS-CoV-2, has been found to possess a very close association with Bat-CoV RaTG13 and Pangolin-CoV MP789. The nucleocapsid protein can serve as a decent model for determining phylogenetic, evolutionary, and structural relationships between coronaviruses. Therefore, this study uses the nucleocapsid gene and protein to further investigate the relationship between SARS-CoV-2 and closely related bat and pangolin coronaviruses. Sequence and phylogenetic analyses have revealed the nucleocapsid gene and protein in SARS-CoV-2 are both closely related to those found in Bat-CoV RaTG13 and Pangolin-CoV MP789. Evidence of recombination was detected within the N gene, along with the presence of a double amino acid insertion found in the N-terminal region. Homology modeling for the N-Terminal Domain revealed similar structures but distinct electrostatic surfaces and topological variations in the β-hairpin that likely reflect specific adaptive functions. In respect to SARS-CoV-2, two amino acids (S37 and A267) were found to exist only in its N protein, along with an extended β-hairpin that bends towards the nucleotide binding site. Collectively, this study strengthens the relationship among SARS-CoV-2, Bat-CoV RaTG13, and Pangolin-CoV MP789, providing additional insights into the structure and adaptive nature of the nucleocapsid protein found in these coronaviruses. Furthermore, these data will enhance our understanding of the complete history behind SARS-CoV-2 and help assist in antiviral and vaccine development.


Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 366 ◽  
Author(s):  
Ying He ◽  
Bingxia Lu ◽  
Kiril M. Dimitrov ◽  
Jiaxing Liang ◽  
Zhongwei Chen ◽  
...  

Newcastle disease is an important poultry disease that also affects Columbiform birds. The viruses adapted to pigeons and doves are referred to as pigeon paramyxoviruses 1 (PPMV-1). PPMV-1 are frequently isolated from pigeons worldwide and have the potential to cause disease in chickens. The complete genomes of 18 PPMV-1 isolated in China during 2012–2018 were sequenced by next-generation sequencing (NGS). Comprehensive phylogenetic analyses showed that five of the viruses belong to sub-genotype VI1.2.1.1.2.1 and 13 isolates belong to sub-genotype VI.2.1.1.2.2. The results demonstrate that these sub-genotypes have been predominant in China during the last decade. The viruses of these sub-genotypes have been independently maintained and continuously evolved for over 20 years, and differ significantly from those causing outbreaks worldwide during the 1980s to 2010s. The viral reservoir remains unknown and possibilities of the viruses being maintained in both pigeon farms and wild bird populations are viable. In vivo characterization of the isolates’ pathogenicity estimated mean death times between 62 and 114 h and intracerebral pathogenicity indices between 0.00 and 0.63. Cross-reactivity testing showed minor antigenic differences between the studied viruses and the genotype II LaSota vaccine. These data will facilitate PPMV-1 epidemiology studies, vaccine development, and control of Newcastle disease in pigeons and poultry.


Author(s):  
Mark David Walker ◽  
Mihály Sulyok

Abstract Background Restrictions on social interaction and movement were implemented by the German government in March 2020 to reduce the transmission of coronavirus disease 2019 (COVID-19). Apple's “Mobility Trends” (AMT) data details levels of community mobility; it is a novel resource of potential use to epidemiologists. Objective The aim of the study is to use AMT data to examine the relationship between mobility and COVID-19 case occurrence for Germany. Is a change in mobility apparent following COVID-19 and the implementation of social restrictions? Is there a relationship between mobility and COVID-19 occurrence in Germany? Methods AMT data illustrates mobility levels throughout the epidemic, allowing the relationship between mobility and disease to be examined. Generalized additive models (GAMs) were established for Germany, with mobility categories, and date, as explanatory variables, and case numbers as response. Results Clear reductions in mobility occurred following the implementation of movement restrictions. There was a negative correlation between mobility and confirmed case numbers. GAM using all three categories of mobility data accounted for case occurrence as well and was favorable (AIC or Akaike Information Criterion: 2504) to models using categories separately (AIC with “driving,” 2511. “transit,” 2513. “walking,” 2508). Conclusion These results suggest an association between mobility and case occurrence. Further examination of the relationship between movement restrictions and COVID-19 transmission may be pertinent. The study shows how new sources of online data can be used to investigate problems in epidemiology.


2021 ◽  
Vol 147 (4) ◽  
pp. 1007-1017
Author(s):  
Branka Powter ◽  
Sarah A. Jeffreys ◽  
Heena Sareen ◽  
Adam Cooper ◽  
Daniel Brungs ◽  
...  

AbstractThe TERT promoter (pTERT) mutations, C228T and C250T, play a significant role in malignant transformation by telomerase activation, oncogenesis and immortalisation of cells. C228T and C250T are emerging as important biomarkers in many cancers including glioblastoma multiforme (GBM), where the prevalence of these mutations is as high as 80%. Additionally, the rs2853669 single nucleotide polymorphism (SNP) may cooperate with these pTERT mutations in modulating progression and overall survival in GBM. Using liquid biopsies, pTERT mutations, C228T and C250T, and other clinically relevant biomarkers can be easily detected with high precision and sensitivity, facilitating longitudinal analysis throughout therapy and aid in cancer patient management.In this review, we explore the potential for pTERT mutation analysis, via liquid biopsy, for its potential use in personalised cancer therapy. We evaluate the relationship between pTERT mutations and other biomarkers as well as their potential clinical utility in early detection, prognostication, monitoring of cancer progress, with the main focus being on brain cancer.


Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 667
Author(s):  
Robert J. Geraghty ◽  
Matthew T. Aliota ◽  
Laurent F. Bonnac

The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 1 and 2 (SARS and SARS-CoV-2) viruses, or new strains of influenza represents significant human health threats due to the absence of available treatments. Vaccines represent a key answer to control these viruses. However, in the case of a public health emergency, vaccine development, safety, and partial efficacy concerns may hinder their prompt deployment. Thus, developing broad-spectrum antiviral molecules for a fast response is essential to face an outbreak crisis as well as for bioweapon countermeasures. So far, broad-spectrum antivirals include two main categories: the family of drugs targeting the host-cell machinery essential for virus infection and replication, and the family of drugs directly targeting viruses. Among the molecules directly targeting viruses, nucleoside analogues form an essential class of broad-spectrum antiviral drugs. In this review, we will discuss the interest for broad-spectrum antiviral strategies and their limitations, with an emphasis on virus-targeted, broad-spectrum, antiviral nucleoside analogues and their mechanisms of action.


2021 ◽  
Vol 22 (5) ◽  
pp. 2723
Author(s):  
Linhua Tian ◽  
Elzafir B. Elsheikh ◽  
Paul N. Patrone ◽  
Anthony J. Kearsley ◽  
Adolfas K. Gaigalas ◽  
...  

Quantitative and robust serology assays are critical measurements underpinning global COVID-19 response to diagnostic, surveillance, and vaccine development. Here, we report a proof-of-concept approach for the development of quantitative, multiplexed flow cytometry-based serological and neutralization assays. The serology assays test the IgG and IgM against both the full-length spike antigens and the receptor binding domain (RBD) of the spike antigen. Benchmarking against an RBD-specific SARS-CoV IgG reference standard, the anti-SARS-CoV-2 RBD antibody titer was quantified in the range of 37.6 µg/mL to 31.0 ng/mL. The quantitative assays are highly specific with no correlative cross-reactivity with the spike proteins of MERS, SARS1, OC43 and HKU1 viruses. We further demonstrated good correlation between anti-RBD antibody titers and neutralizing antibody titers. The suite of serology and neutralization assays help to improve measurement confidence and are complementary and foundational for clinical and epidemiologic studies.


Insects ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 232
Author(s):  
Nan Zhou ◽  
Yanling Dong ◽  
Pingping Qiao ◽  
Zhaofu Yang

To understand mitogenome characteristics and reveal phylogenetic relationships of the genus Ostrinia, including several notorious pests of great importance for crops, we sequenced the complete mitogenomes of four species: Ostrinia furnacalis (Guenée, 1854), Ostrinia nubilalis (Hübner, 1796), Ostrinia scapulalis (Walker, 1859) and Ostrinia zealis (Guenée, 1854). Results indicate that the four mitogenomes—O. furnacalis, O. nubilalis, O. scapulalis, and O. zealis—are 15,245, 15,248, 15,311, and 15,208 bp in size, respectively. All four mitogenomes are comprised of 37 encoded genes and a control region. All 13 protein-coding genes (PCGs) initiate with ATN and terminate with TAN, with the exception of cox1 that starts with CGA, and cox1, cox2, and nad5 that terminate with an incomplete codon T. All transfer RNA genes (tRNAs) present the typical clover-leaf secondary structure except for the trnS1 (AGN) gene. There are some conserved structural elements in the control region. Our analyses indicate that nad6 and atp6 exhibit higher evolution rates compared to other PCGs. Phylogenetic analyses based on mitogenomes using both maximum likelihood (ML) and Bayesian inference (BI) methods revealed the relationship (O. palustralis + (O. penitalis + (O. zealis + (O. furnacalis + (O. nubilalis + O. scapulalis))))) within Ostrinia.


Author(s):  
M. Belaganahalli ◽  
S. Maan ◽  
P. P.C. Mertens

Viruses that are normally safely contained within their host spe­cies can emerge due to intense livestock farming, trade, travel, climate change and encroachment of human activities into new environments. The unexpected emergence of bluetongue virus (BTV), the prototype species of the genus Orbivirus, in economi­cally important livestock species (sheep and cattle) across the whole of Europe (since 1998), indicates that other orbiviruses represent a potential further threat to animal and human popula­tions in Europe and elsewhere. The genus Orbivirus is the largest within the family Reoviridae, containing 22 virus species, as well as 14 unclassified orbiviruses, some of which may repre­sent additional or novel species. The orbiviruses are transmitted primarily by arthropod vectors (e.g. Culicoides, mosquitoes or ticks).  Viral genome sequence data provide a basis for virus taxonomy and diagnostic test development, and make it possible to address fundamental questions concerning virus biology, pathogenesis, virulence and evolution, that can be further explored in mutation and reverse genetics studies. Genome sequences also provide criteria for the classification of novel isolates within individual Orbivirus species, as well as the identification of different sero­types, topotypes, reassortants and even closely related but dis­tinct virus lineages.  Full-length genome characterization of Tilligerry virus (TILV), a member of the Eubenangee virus species, and Mitchell River virus (MRV), a member of the Warrego virus species, have revealed highly conserved 5’ and 3’ terminal hexanucleotide sequences. Phylogenetic analyses of orbivirus T2 ‘sub-core-shell’ protein sequences reinforce the hypothesis that this protein is an important evolutionary marker for these viruses. The T2 protein shows high levels of amino acid (AA) sequence identity (> 91%) within a single Orbivirus species / serogroup, which can be used for species identification. The T2-protein gene has therefore been given priority in sequencing studies. The T2 protein of TILV is closely related to that of Eubenangee virus (~91% identity), con­firming that they are both members of the same Eubenangee virus species. Although TILV is reported to be related to BTV in serological assays, the TILV T2 protein shows only 68-70% AA identity to BTV. This supports its current classification within a different serogroup (Eubenangee).  Warrego virus and MRV are currently classified as two distinct members (different serotypes) within the Warrego virus species. However, they show only about 79% AA identity in their T2 pro­tein (based on partial sequences). It is therefore considered likely that they could be reclassified as members of distinct Orbivirus species. The taxonomic classification of MRV will be reviewed after generating full length sequences for the entire genomes of both viruses. The taxonomic status of each of these viruses will also be tested further by co-infections and attempts to create reassortants between them (only viruses belonging to the same species can reassort their genome segments). TILV and MRV are the first viruses from their respective serogroups / virus species to be genetically fully characterized, and will provide a basis for the further characterization / identification of additional viruses within each group / species. These data will assist in the devel­opment of specific diagnostic assays and potentially in control of emerging diseases. The sequences generated will also help to evaluate current diagnostic [reverse transcriptase - polymerase chain reaction (RT-PCR)] tests for BTV, African horse sickness virus, epizootic haemorrhagic disease virus, etc., in silico, by identifying any possibility of cross reactivity.


Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1021
Author(s):  
Ayobami Adegbite ◽  
Pumtiwitt C. McCarthy

Vaccines are important in preventing disease outbreaks and controlling the spread of disease in a population. A variety of vaccines exist, including subunit, recombinant, and conjugate vaccines. Glycoconjugate vaccines have been an important tool to fight against diseases caused by a number of bacteria. Glycoconjugate vaccines are often heterogeneous. Vaccines of the future are becoming more rationally designed to have a defined oligosaccharide chain length and position of conjugation. Homogenous vaccines could play an important role in assessing the relationship between vaccine structure and immune response. This review focuses on recent advances in the chemoenzymatic production of defined bacterial oligosaccharides for vaccine development with a focus on Neisseria meningitidis and selected WHO-prioritized antibacterial resistant-pathogens. We also provide some perspective on future advances in the chemoenzymatic synthesis of well-defined oligosaccharides.


F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 1875
Author(s):  
Maria del Pilar Martinez Viedma ◽  
Nurgun Kose ◽  
Leda Parham ◽  
Angel Balmaseda ◽  
Guillermina Kuan ◽  
...  

Background: Global outbreaks caused by emerging or re-emerging arthropod-borne viruses (arboviruses) are becoming increasingly more common. These pathogens include the mosquito-borne viruses belonging to the Flavivirus and Alphavirus genera. These viruses often cause non-specific or asymptomatic infection, which can confound viral prevalence studies. In addition, many acute phase diagnostic tests rely on the detection of viral components such as RNA or antigen. Standard serological tests are often not reliable for diagnosis after seroconversion and convalescence due to cross-reactivity among flaviviruses. Methods: In order to contribute to development efforts for mosquito-borne serodiagnostics, we incubated 137 human sera on individual custom peptide arrays that consisted of over 866 unique peptides in quadruplicate. Our bioinformatics workflow to analyze these data incorporated machine learning, statistics, and B-cell epitope prediction. Results: Here we report the results of our peptide array data analysis, which revealed sets of peptides that have diagnostic potential for detecting past exposure to a subset of the tested human pathogens including Zika virus. These peptides were then confirmed using the well-established ELISA method. Conclusions: These array data, and the resulting peptides can be useful in diverse efforts including the development of new pan-flavivirus antibodies, more accurate epitope mapping, and vaccine development against these viral pathogens.


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