Determination of the coding and non-coding nucleotide sequences of genuine Edmonston–Zagreb master seed and current working seed lot

Baričević, Marijana; Forčić, Dubravko; Gulija, Tanja Košutić; Jug, Renata; Mažuran, Renata

doi:10.1016/j.vaccine.2004.08.021

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…The genetic stability of measles is exceptionally high, and it has been observed that it undergoes remarkably little sequence variation over long periods of time, both in laboratory settings and in the field. In several studies on MeV genetic stability, comparison of genomic sequences obtained after passaging in vitro revealed either complete sequence identity with the seed stock [ 37 , 38 ] or a single nucleotide change between two working stocks that had a widely divergent passage history [ 39 ]. Even the most variable sequence in the MeV genome, N-450, appears to be very stable over the course of in vitro passaging, irrespective of the cell type used for growth [ 39 ].…”

Section: High Genetic Stability Of Mev In the Lab And In The Fieldmentioning

confidence: 99%

Constraints on the Genetic and Antigenic Variability of Measles Virus

Beaty

Lee

2016

Viruses

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Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the field, and few regions of the genome allow for rapid genetic change. The regions of the genome that are more tolerant of mutations (i.e., the untranslated regions and certain domains within the N, C, V, P, and M proteins) indicate genetic plasticity or structural flexibility in the encoded proteins. Our analysis reveals that strong constraints in the envelope proteins (F and H) allow for a single serotype despite known antigenic differences among its 24 genotypes. This review describes some of the many variables that limit the evolutionary rate of MeV. The high genomic stability of MeV appears to be a shared property of the Paramyxovirinae, suggesting a common mechanism that biologically restricts the rate of mutation.

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Section: High Genetic Stability Of Mev In the Lab And In The Fieldmentioning

confidence: 99%

Constraints on the Genetic and Antigenic Variability of Measles Virus

Beaty

Lee

2016

Viruses

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“…RNA was extracted and used to obtain a consensus sequence of the complete viral genome, including the 3= and 5= ends, which were sequenced following RACE. The sequence was identical to the previously published MV EZ master and working seed stock sequences (GenBank accession numbers AY486083.1 and AY486084.1 (22). Subsequently, a full-length anti-genomic plasmid (pMV EZ ) was constructed.…”

Section: Generation and Characterization Of Recombinant Virusesmentioning

confidence: 99%

Live-Attenuated Measles Virus Vaccine Targets Dendritic Cells and Macrophages in Muscle of Nonhuman Primates

Rennick

Vries

Carsillo

et al. 2015

J Virol

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Although live-attenuated measles virus (MV) vaccines have been used successfully for over 50 years, the target cells that sustain virus replication in vivo are still unknown. We generated a reverse genetics system for the live-attenuated MV vaccine strain Edmonston-Zagreb ( IMPORTANCE Even though MV strain Edmonston-Zagreb has long been used as a live-attenuated vaccine (LAV) to protect against measles, nothing is known about the primary cells in which the virus replicates in vivo.This is vital information given the push to move toward needle-free routes of vaccination, since vaccine virus replication is essential for vaccination efficacy. We have generated a number of recombinant MV strains expressing enhanced green fluorescent protein. The virus that best mimicked the nonrecombinant vaccine virus was formulated according to protocols for production of commercial vaccine virus batches, and was subsequently used to assess viral tropism in nonhuman primates. The virus primarily replicated in professional antigen-presenting cells, which may explain why this LAV is so immunogenic and efficacious.

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“…These observations motivated us to compare the C protein functions between the IC-B and Edmonston tag strains in the context of virus infection. It should be noted that the licensed, highly attenuated Zagreb vaccine strain encodes a C protein with an amino acid sequence identical to that of the Edmonston tag strain (4,27). However, analyses of the C protein using infectious MVs pose the problem that mutations in the C protein are often accompanied by mutations in the P and V proteins because they are encoded in overlapping reading frames.…”

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confidence: 99%

A Highly Attenuated Measles Virus Vaccine Strain Encodes a Fully Functional C Protein

Nakatsu

Takeda

Iwasaki

et al. 2009

J Virol

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The P, V, and C proteins of measles virus are encoded in overlapping reading frames of the P gene, which makes it difficult to analyze the functions of the individual proteins in the context of virus infection. We established a system to analyze the C protein independently from the P and V proteins by placing its gene in an additional transcription unit between the H and L genes. Analyses with this system indicated that a highly attenuated Edmonston lineage vaccine strain encodes a fully functional C protein, and the P and/or V protein is involved in the attenuated phenotype.Measles is a highly contagious disease characterized by high fever and a maculopapular rash. About 4% of deaths in children aged under 5 years are caused by measles worldwide (9). The causative agent, measles virus (MV), belongs to the genus Morbillivirus in the family Paramyxoviridae. The genome of MV is a nonsegmented negative-strand RNA of ϳ16 kb in length and contains six genes. Each gene encodes a single structural protein, namely the nucleocapsid (N), phospho (P), matrix (M), fusion (F), hemagglutinin (H), and large (L) proteins (17). The genome forms a helical ribonucleoprotein complex with the N protein and viral RNAdependent RNA polymerase composed of the P and L proteins. The P protein acts as an essential cofactor of RNA-dependent RNA polymerase and tethers the L protein onto the nucleocapsid template (20). The P gene encodes additional gene products, the V and C proteins, by the processes of RNA editing and alternative translational initiation in a different reading frame, respectively (17). Although the V and C proteins are nonessential for MV replication (29, 35), they act as important virulence factors in vivo (11,28,(44)(45)(46). Many lines of evidence have indicated that the C and V proteins of MV antagonize the host interferon (IFN) responses (10,16,22,23,25,26,37,42,47). The V protein directly interferes with pathways of IFN induction (1) and IFN signaling (25,26,42), while the C protein contributes to circumvention of IFN induction by controlling the levels of viral RNA synthesis (22,23,31). Direct interference with IFN signaling by the C protein has also been reported, although its effects are weaker than those of the V protein (16,37).In a recent study, we showed that a recombinant IC-B strain possessing the P gene of the attenuated Edmonston tag strain (IC/EdP) replicates less efficiently than the parental IC-B strain (a virulent strain) (40). The Edmonston tag strain is a recombinant MV derived from the Edmonston B vaccine strain, which has been passaged numerous times in various cultured cells (30). There are many amino acid differences between the P gene products of the IC-B and Edmonston tag strains ( Fig. 1) (27,30,43). Most of the changes found in the Edmonston tag strain are common to the Edmonston lineage MV strains (27). However, owing to two amino acid substitutions at positions 110 and 272, which are not conserved among the Edmonston lineage MV strains (25-27), the V protein of the Edmonston tag strain is de...

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Determination of the coding and non-coding nucleotide sequences of genuine Edmonston–Zagreb master seed and current working seed lot

Cited by 7 publications

References 11 publications

Constraints on the Genetic and Antigenic Variability of Measles Virus

Constraints on the Genetic and Antigenic Variability of Measles Virus

Live-Attenuated Measles Virus Vaccine Targets Dendritic Cells and Macrophages in Muscle of Nonhuman Primates

A Highly Attenuated Measles Virus Vaccine Strain Encodes a Fully Functional C Protein

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