The Genome Nucleotide Sequence of a Contemporary Wild Strain of Measles Virus and Its Comparison with the Classical Edmonston Strain Genome

Abstract

The only complete genome nucleotide sequences of measles virus (MeV) reported to date have been for the Edmonston (Ed) strain and derivatives, which were isolated decades ago, passaged extensively under laboratory conditions, and appeared to be nonpathogenic. Partial sequencing of many other strains has identified >/=15 genotypes. Most recent isolates, including those typically pathogenic, belong to genotypes distinct from the Edmonston type. Therefore, the sequence of Ed and related strains may not be representative of those of pathological measles circulating at that or any time in human populations. Taking into account these issues as well as the fact that so many studies have been based upon Ed-related strains, we have sequenced the entire genome of a recently isolated pathogenic strain, 9301B. Between this recent isolate and the classical Ed strain, there were 465 nucleotide differences (2.93%) and 114 amino acid differences (2.19%). Computation of nonsynonymous and synonymous substitutions in open reading frames as well as direct comparisons of noncoding regions of each gene and extracistronic regulatory regions clearly revealed the regions where changes have been permissible and nonpermissible. Notably, considerable nonsynonymous substitutions appeared to be permissible for the P frame to maintain a high degree of sequence conservation for the overlapping C frame. However, the cause and the effect were largely unclear for any substitution, indicating that there is a considerable gap between the two strains that cannot be filled. The sequence reported here would be useful as a reference of contemporary wild-type MeV.

A Human Lung Carcinoma Cell Line Supports Efficient Measles Virus Growth and Syncytium Formation via a SLAM- and CD46-Independent Mechanism

“…1C), indicating that NCI-H358 cells are susceptible and permissive to wt MV at a level similar to that of B95a cells. These observations were confirmed using six clinical isolates of wt MV belonging to genotypes D3 and D5 (37,41). All six strains grew and produced syncytia in NCI-H358 cells, as they do in SLAM-positive cell lines (data not shown).…”

Multiple Amino Acid Substitutions in Hemagglutinin Are Necessary for Wild-Type MeaslesVirus To Acquire the Ability To Use Receptor CD46 Efficiently

“…It has been shown that the amino acid residue at position 481 of the H protein has an important role in determining the receptor usage of MV strains (3,12,20,27,43,53,55,58). The H proteins of most CD46-using strains, including Edmonston vaccine strains, have a tyrosine residue at that position, whereas those of wild-type strains usually have an asparagine residue (3,15,20,32,37,49). Studies have indicated that an asparagine-to-tyrosine substitution at position 481 (N481Y) enables the H proteins of wild-type MV strains to bind CD46, without compromising their ability to use SLAM (8,12,20,58).…”

Measles Viruses Possessing the Polymerase Protein Genes of the Edmonston Vaccine Strain Exhibit Attenuated Gene Expression and Growth in Cultured Cells and SLAM Knock-In Mice

“…Compared with the genomes of wild-type MV strains, the genomes of the Edmonston vaccine strains have three nucleotide substitutions (uracil-to-adenine, uracil-to-guanine, and uracil-to-cytosine changes at nucleotide positions 26, 42, and 50, respectively) in the genomic promoter (leader [Le]) region (16,37). Using minigenome assays, these substitutions have been shown to enhance the promoter activity (16).…”