title: Mutational Analysis of Measles Virus Suggests Constraints on Antigenic Variation of the Glycoproteins.
abstract: Measles virus undergoes error-prone replication like other RNA viruses, but over time, it has remained antigenically monotypic. The constraints on the virus that prevent the emergence of antigenic variants are unclear. As a first step in understanding this question, we subjected the measles virus genome to unbiased insertional mutagenesis, and viruses that could tolerate insertions were rescued. Only insertions in the nucleoprotein, phosphoprotein, matrix protein, as well as intergenic regions were easily recoverable. Insertions in the glycoproteins of measles virus were severely under-represented in our screen. Host immunity depends on developing neutralizing antibodies to the hemagglutinin and fusion glycoproteins; our analysis suggests that these proteins occupy very little evolutionary space and therefore have difficulty changing in the face of selective pressures. We propose that the inelasticity of these proteins prevents the sequence variation required to escape antibody neutralization in the host, allowing for long-lived immunity after infection with the virus.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Benjamin O
authors.initials: BO
authors.lastname: Fulton
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sachs
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Beaty
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Sohui T
authors.initials: ST
authors.lastname: Won
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Benhur
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: nicholas.heaton@mssm.edu.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Heaton
mesh_terms: D000940:Antigenic Variation; D000956:Antigens, Viral / Q000235:genetics*; D004252:DNA Mutational Analysis; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008459:Measles virus / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D014764:Viral Proteins