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Mutational Analysis of Measles Virus Suggests Constraints on Antigenic Variation of the Glycoproteins.

Publication ,  Journal Article
Fulton, BO; Sachs, D; Beaty, SM; Won, ST; Lee, B; Palese, P; Heaton, NS
Published in: Cell Rep
June 9, 2015

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.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

June 9, 2015

Volume

11

Issue

9

Start / End Page

1331 / 1338

Location

United States

Related Subject Headings

  • Viral Proteins
  • Transfection
  • Mutagenesis, Site-Directed
  • Measles virus
  • Humans
  • Glycoproteins
  • DNA Mutational Analysis
  • Antigens, Viral
  • Antigenic Variation
  • 31 Biological sciences
 

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Fulton, B. O., Sachs, D., Beaty, S. M., Won, S. T., Lee, B., Palese, P., & Heaton, N. S. (2015). Mutational Analysis of Measles Virus Suggests Constraints on Antigenic Variation of the Glycoproteins. Cell Rep, 11(9), 1331–1338. https://doi.org/10.1016/j.celrep.2015.04.054
Fulton, Benjamin O., David Sachs, Shannon M. Beaty, Sohui T. Won, Benhur Lee, Peter Palese, and Nicholas S. Heaton. “Mutational Analysis of Measles Virus Suggests Constraints on Antigenic Variation of the Glycoproteins.Cell Rep 11, no. 9 (June 9, 2015): 1331–38. https://doi.org/10.1016/j.celrep.2015.04.054.
Fulton BO, Sachs D, Beaty SM, Won ST, Lee B, Palese P, et al. Mutational Analysis of Measles Virus Suggests Constraints on Antigenic Variation of the Glycoproteins. Cell Rep. 2015 Jun 9;11(9):1331–8.
Fulton, Benjamin O., et al. “Mutational Analysis of Measles Virus Suggests Constraints on Antigenic Variation of the Glycoproteins.Cell Rep, vol. 11, no. 9, June 2015, pp. 1331–38. Pubmed, doi:10.1016/j.celrep.2015.04.054.
Fulton BO, Sachs D, Beaty SM, Won ST, Lee B, Palese P, Heaton NS. Mutational Analysis of Measles Virus Suggests Constraints on Antigenic Variation of the Glycoproteins. Cell Rep. 2015 Jun 9;11(9):1331–1338.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

June 9, 2015

Volume

11

Issue

9

Start / End Page

1331 / 1338

Location

United States

Related Subject Headings

  • Viral Proteins
  • Transfection
  • Mutagenesis, Site-Directed
  • Measles virus
  • Humans
  • Glycoproteins
  • DNA Mutational Analysis
  • Antigens, Viral
  • Antigenic Variation
  • 31 Biological sciences