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Molecular characterization of measles virus strains causing subacute sclerosing panencephalitis in France in 1977 and
Emilie Moulin1, Vanda Beal, Damien Jeantet
1National Reference Center for Measles, Lyon, France; Immunobiology of Viral Infections, Inserm, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; IFR128 BioSciences Lyon-Gerland Lyon-Sud, Lyon, France; University of Lyon, Lyon, France.
Abstract:
Measles virus strains from two subacute sclerosing panencephalitis (SSPE) cases diagnosed in 1977 (Laine strain) and in 2007 (Hoedts strain) were studied. Phylogenetic analysis based on C-terminal part of the nucleoprotein and the entire H gene showed that Hoedts strain, circulating in France presumably in the 1980s, belonged to genotype C2. However, Laine strain, suspected to have circulated between 1940s and 1960s, could not be assigned to any known measles virus genotypes. Sequences analysis of the Laine strain suggested that it originated from a measles virus that may have circulating at the same period as the Edmonston strain. The analysis of the whole genome of both SSPE strains revealed biased hypermutations in M, F, and H gene. Some of these mutations like the L165P found in the M protein sequence of the Laine strain, the amino acid position 94, where a mutation M94V was found in the F protein sequence of the Hoedts strain are known to play an important role in the glycoprotein interaction and to impair the ability of measles virus strain to produce cell-free infectious viral particles.This is the first study on molecular characterization of the entire coding region of measles virus isolated from SSPE cases in France.
Insights
This study characterized measles virus strains from subacute sclerosing panencephalitis (SSPE) cases in France. One strain belonged to genotype C2, while another represented a potentially novel genotype, revealing unique mutations impacting viral particle production.
Area of Science:
- Virology
- Genetics
- Neuroscience
Background:
- Subacute sclerosing panencephalitis (SSPE) is a rare, fatal neurological complication of measles virus infection.
- Understanding the genetic diversity and evolution of measles virus strains associated with SSPE is crucial for disease pathogenesis research.
Observation:
- Two measles virus strains, Laine (1977) and Hoedts (2007), isolated from French SSPE cases were analyzed.
- Phylogenetic analysis placed the Hoedts strain within genotype C2, while the Laine strain could not be assigned to known genotypes, suggesting a potential historical lineage.
- Whole-genome analysis revealed significant hypermutations in the M, F, and H genes of both strains, including specific mutations known to affect viral glycoprotein interactions.
Findings:
- The Hoedts strain, likely circulating in the 1980s, aligns with genotype C2.
- The Laine strain, potentially circulating from the 1940s-1960s, exhibits characteristics distinct from currently defined measles virus genotypes.
- Identified mutations, such as L165P in the M protein (Laine) and M94V in the F protein (Hoedts), are implicated in impaired cell-free infectious viral particle production.
Implications:
- This research provides the first molecular characterization of the complete coding region of measles virus from French SSPE cases.
- The findings contribute to understanding measles virus evolution and the genetic factors underlying SSPE pathogenesis.
- The identification of potentially novel genotypes and specific mutations offers insights into viral adaptation and disease mechanisms.
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