Cross-Neutralization between Human and African Bat Mumps Viruses.
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ABSTRACT:
SUBMITTER: Katoh H
PROVIDER: S-EPMC4806932 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses.By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes.All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains.Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates.
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Project description:To evaluate the antigenic relationship between bat mumps virus (BMV) and the JL5 vaccine strain of mumps virus (MuVJL5), we rescued a chimeric virus bearing the F and HN glycoproteins of BMV in the background of a recombinant JL5 genome (rMuVJL5). Cross-reactivity and cross-neutralization between this chimeric recombinant MuV bearing the F and HN glycoproteins of BMV (rMuVJL5-F/HNBMV) virus and rMuVJL5 were demonstrated using hyperimmune mouse serum samples and a curated panel of human serum. All mouse and human serum samples that were able to neutralize rMuVJL5 infection had cross-neutralizing activity against rMuVJL5-F/HNBMV. Our data suggest that persons who have neutralizing antibodies against MuV might be protected from infection by BMV.
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Project description:The straw-coloured fruit bat, Eidolon helvum, is Africa's most widely distributed and commonly hunted fruit bat, often living in close proximity to human populations. This species has been identified as a reservoir of potentially zoonotic viruses, but uncertainties remain regarding viral transmission dynamics and mechanisms of persistence. Here we combine genetic and serological analyses of populations across Africa, to determine the extent of epidemiological connectivity among E. helvum populations. Multiple markers reveal panmixia across the continental range, at a greater geographical scale than previously recorded for any other mammal, whereas populations on remote islands were genetically distinct. Multiple serological assays reveal antibodies to henipaviruses and Lagos bat virus in all locations, including small isolated island populations, indicating that factors other than population size and connectivity may be responsible for viral persistence. Our findings have potentially important public health implications, and highlight a need to avoid disturbances that may precipitate viral spillover.
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Project description:In 2016, a year-long large-scale mumps outbreak occurred in Arkansas among a highly-vaccinated population. A total of 2954 mumps cases were identified during this outbreak. The majority of cases (1676 (57%)) were school-aged children (5-17 years), 1536 (92%) of these children had completed the mumps vaccination schedule. To weigh the possibility that the mumps virus evaded vaccine-induced immunity in the affected Arkansas population, we established a pipeline for genomic characterization of the outbreak strains. Our pipeline produces whole-genome sequences along with phylogenetic analysis of the outbreak mumps virus strains. We collected buccal swab samples of patients who tested positive for the mumps virus during the 2016 Arkansas outbreak, and used the portable Oxford Nanopore Technology to sequence the extracted strains. Our pipeline identified the genotype of the Arkansas mumps strains as genotype G and presented a genome-based phylogenetic tree with superior resolution to a standard small hydrophobic (SH) gene-based tree. We phylogenetically compared the Arkansas whole-genome sequences to all publicly available mumps strains. While these analyses show that the Arkansas mumps strains are evolutionarily distinct from the vaccine strains, we observed no correlation between vaccination history and phylogenetic grouping. Furthermore, we predicted potential B-cell epitopes encoded by the Arkansas mumps strains using a random forest prediction model trained on antibody-antigen protein structures. Over half of the predicted epitopes of the Jeryl-Lynn vaccine strains in the Hemagglutinin-Neuraminidase (HN) surface glycoprotein (a major target of neutralizing antibodies) region are missing in the Arkansas mumps strains. In-silico analyses of potential epitopes may indicate that the Arkansas mumps strains display antigens with reduced immunogenicity, which may contribute to reduced vaccine effectiveness. However, our in-silico findings should be assessed by robust experiments such as cross neutralization assays. Metadata analysis showed that vaccination history had no effect on the evolution of the Arkansas mumps strains during this outbreak. We conclude that the driving force behind the spread of the mumps virus in the 2016 Arkansas outbreak remains undetermined.
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