About: Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate

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About: Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate
Creator	Enjuanes, Luis Sola, Isabel Almazán, Fernando Marquez-Jurado, Silvia Zuñiga, Sonia Andrés, German Buchmeier, Michael Dediego, Marta Nieto-Torres, Jose
Source	Medline; PMC
abstract	Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus infecting humans that is associated with acute pneumonia, occasional renal failure, and a high mortality rate and is considered a threat to public health. The construction of a full-length infectious cDNA clone of the MERS-CoV genome in a bacterial artificial chromosome is reported here, providing a reverse genetics system to study the molecular biology of the virus and to develop attenuated viruses as vaccine candidates. Following transfection with the cDNA clone, infectious virus was rescued in both Vero A66 and Huh-7 cells. Recombinant MERS-CoVs (rMERS-CoVs) lacking the accessory genes 3, 4a, 4b, and 5 were successfully rescued from cDNA clones with these genes deleted. The mutant viruses presented growth kinetics similar to those of the wild-type virus, indicating that accessory genes were not essential for MERS-CoV replication in cell cultures. In contrast, an engineered mutant virus lacking the structural E protein (rMERS-CoV-ΔE) was not successfully rescued, since viral infectivity was lost at early passages. Interestingly, the rMERS-CoV-ΔE genome replicated after cDNA clone was transfected into cells. The infectious virus was rescued and propagated in cells expressing the E protein in trans, indicating that this virus was replication competent and propagation defective. Therefore, the rMERS-CoV-ΔE mutant virus is potentially a safe and promising vaccine candidate to prevent MERS-CoV infection. IMPORTANCE Since the emergence of MERS-CoV in the Arabian Peninsula during the summer of 2012, it has already spread to 10 different countries, infecting around 94 persons and showing a mortality rate higher than 50%. This article describes the development of the first reverse genetics system for MERS-CoV, based on the construction of an infectious cDNA clone inserted into a bacterial artificial chromosome. Using this system, a collection of rMERS-CoV deletion mutants has been generated. Interestingly, one of the mutants with the E gene deleted was a replication-competent, propagation-defective virus that could only be grown in the laboratory by providing E protein in trans, whereas it would only survive a single virus infection cycle in vivo. This virus constitutes a vaccine candidate that may represent a balance between safety and efficacy for the induction of mucosal immunity, which is needed to prevent MERS-CoV infection.
has issue date	2013-09-10(xsd:dateTime)
bibo:doi	10.1128/mbio.00650-13
bibo:pmid	24023385
has license	cc-by-nc-sa
sha1sum (hex)	71b1e5b3dcbccd130699fbbdbc537a66a24598bc
schema:url	https://doi.org/10.1128/mbio.00650-13
resource representing a document's title	Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate
has PubMed Central identifier	PMC3774192
has PubMed identifier	24023385
schema:publication	mBio
resource representing a document's body	covid:71b1e5b3dcbccd130699fbbdbc537a66a24598bc#body_text
is schema:about of	named entity 'MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS' named entity 'DEFECTIVE' named entity 'VACCINE CANDIDATE' named entity 'E PROTEIN' named entity 'CORONAVIRUS' named entity 'A66' named entity 'VIRUSES' named entity 'VERO' named entity 'ACUTE PNEUMONIA' named entity 'MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS' named entity 'INFECTIVITY' named entity 'PUBLIC HEALTH' named entity 'MORTALITY RATE' named entity 'GENOME' named entity 'DELETED' named entity 'TRANSFECTION' named entity 'VACCINE' named entity 'GENES' named entity 'REVERSE GENETICS' named entity 'HUMANS' named entity 'EARLY' named entity 'STUDY' named entity 'ASSOCIATED WITH' named entity 'REPLICATION' named entity 'HUH-7' named entity 'SYSTEM' named entity 'clone' named entity 'A66' named entity 'passages' named entity 'structural' named entity 'Huh' named entity 'transfected' named entity 'wild-type' named entity 'presented' named entity 'protein' named entity 'develop' named entity 'LACKING' named entity 'CONSIDERED' named entity 'ENGINEERING' named entity 'ENGINEERED' named entity 'HERE' named entity 'PRESENTED' named entity 'MOLECULAR BIOLOGY' named entity 'CONTRAST' named entity 'INDICATING' named entity 'CELLS' named entity 'THESE' named entity 'REPLICATION' named entity 'COMPETENT' named entity 'PROPAGATION' named entity 'RECOMBINANT' named entity 'PROTEIN ' named entity 'CONSTRUCTION' named entity 'SIMILAR' named entity 'OCCASIONAL' named entity 'INFECTIOUS' named entity 'INFECTING' named entity 'MUTANT' named entity 'TYPE VIRUS' named entity 'ACCESSORY' named entity 'BACTERIAL ARTIFICIAL CHROMOSOME' named entity 'WILD-TYPE' named entity 'MERS' named entity 'GROWTH KINETICS' named entity 'STRUCTURAL' named entity 'CDNA' named entity 'LENGTH' named entity 'VIRUS' named entity 'REPLICATED' named entity 'ACE' named entity 'THREAT' named entity 'CDNA CLONE' named entity 'PROVIDING'

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