About: Assembly of Replication-Incompetent African Horse Sickness Virus Particles: Rational Design of Vaccines for All Serotypes

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Assembly of Replication-Incompetent African Horse Sickness Virus Particles: Rational Design of Vaccines for All Serotypes
Creator	Beer, Martin Lulla, Aleksei Lulla, Valeria Aebischer, Andrea Roy, Polly Wernike, Kerstin
Source	Medline; PMC
abstract	African horse sickness virus (AHSV), an orbivirus in the Reoviridae family with nine different serotypes, causes devastating disease in equids. The virion particle is composed of seven proteins organized in three concentric layers, an outer layer made of VP2 and VP5, a middle layer made of VP7, and inner layer made of VP3 that encloses a replicase complex of VP1, VP4, and VP6 and a genome of 10 double-stranded RNA segments. In this study, we sought to develop highly efficacious candidate vaccines against all AHSV serotypes, taking into account not only immunogenic and safety properties but also virus productivity and stability parameters, which are essential criteria for vaccine candidates. To achieve this goal, we first established a highly efficient reverse genetics (RG) system for AHSV serotype 1 (AHSV1) and, subsequently, a VP6-defective AHSV1 strain in combination with in trans complementation of VP6. This was then used to generate defective particles of all nine serotypes, which required the exchange of two to five RNA segments to achieve equivalent titers of particles. All reassortant-defective viruses could be amplified and propagated to high titers in cells complemented with VP6 but were totally incompetent in any other cells. Furthermore, these replication-incompetent AHSV particles were demonstrated to be highly protective against homologous virulent virus challenges in type I interferon receptor (IFNAR)-knockout mice. Thus, these defective viruses have the potential to be used for the development of safe and stable vaccine candidates. The RG system also provides a powerful tool for the study of the role of individual AHSV proteins in virus assembly, morphogenesis, and pathogenesis. IMPORTANCE African horse sickness virus is transmitted by biting midges and causes African horse sickness in equids, with mortality reaching up to 95% in naive horses. Therefore, the development of efficient vaccines is extremely important due to major economic losses in the equine industry. Through the establishment of a highly efficient RG system, replication-deficient viruses of all nine AHSV serotypes were generated. These defective viruses achieved high titers in a cell line complemented with VP6 but failed to propagate in wild-type mammalian or insect cells. Importantly, these candidate vaccine strains showed strong protective efficacy against AHSV infection in an IFNAR(−/−) mouse model.
has issue date	2016-07-27(xsd:dateTime)
bibo:doi	10.1128/jvi.00548-16
bibo:pmid	27279609
has license	cc-by
sha1sum (hex)	1d32215c90a79509e66eb1f6e3e05b077d08ee1b
schema:url	https://doi.org/10.1128/jvi.00548-16
resource representing a document's title	Assembly of Replication-Incompetent African Horse Sickness Virus Particles: Rational Design of Vaccines for All Serotypes
has PubMed Central identifier	PMC4984648
has PubMed identifier	27279609
schema:publication	J Virol
resource representing a document's body	covid:1d32215c90a79509e66eb1f6e3e05b077d08ee1b#body_text
is schema:about of	named entity 'REPLICATION' named entity 'ROLE' covid:arg/1d32215c90a79509e66eb1f6e3e05b077d08ee1b named entity 'SYSTEM' named entity 'VP4' named entity 'PRODUCTIVITY' named entity 'VIRUS ASSEMBLY' named entity 'STABLE' named entity 'EQUIVALENT' named entity 'PROVIDES' named entity 'VACCINES' named entity 'ESTABLISHED' named entity 'VACCINES' named entity 'VP7' named entity 'EFFICIENT' named entity 'VP5' named entity 'GOAL' named entity 'IMMUNOGENIC' named entity 'SEROTYPE' named entity 'INDIVIDUAL' named entity 'REQUIRED' named entity 'STRAIN' named entity 'TOOL' named entity 'COMPLEMENTATION' named entity 'MORPHOGENESIS' named entity 'SAFE' named entity 'PARTICLE' named entity 'DEFECTIVE' named entity 'USED' named entity 'ORBIVIRUS' named entity 'DOUBLE-STRANDED RNA' named entity 'AFRICAN HORSE SICKNESS VIRUS' named entity 'ACCOUNT' named entity 'TOTALLY' named entity 'ASSEMBLY' named entity 'SEROTYPES' named entity 'VIRUS PARTICLES' named entity 'SAFETY' named entity 'CHALLENGES' named entity 'ORGANIZED' named entity 'SEROTYPES' named entity 'REPLICASE' named entity 'PROPERTIES' named entity 'GENERATE' named entity 'CANDIDATE' named entity 'COMBINATION' named entity 'LAYER' named entity 'TYPE I INTERFERON RECEPTOR' named entity 'COULD BE' named entity 'HAVE' named entity 'REPLICATION' named entity 'HIGHLY' named entity 'FAMILY' named entity 'VACCINE' named entity 'SEGMENTS' named entity 'DEVELOPMENT' named entity 'VP1' named entity 'CONCENTRIC' named entity 'POTENTIAL' named entity 'RNA' named entity 'AMPLIFIED' named entity 'VP2' named entity 'REOVIRIDAE' named entity 'DEMONSTRATED' named entity 'OUTER LAYER' named entity 'COMPOSED OF' named entity 'DISEASE' named entity 'SEVEN' named entity 'GENOME' named entity 'MIDDLE' named entity 'PATHOGENESIS' named entity 'INCOMPETENT' named entity 'VIRUS' named entity 'LAYERS' named entity 'AFRICAN HORSE SICKNESS VIRUS' named entity 'STUDY'

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