title: Revealing new measles virus transmission routes by use of sequence analysis of phosphoprotein and hemagglutinin genes.
abstract: With improved measles virus (MV) control, the genetic variability of the MV-nucleoprotein hypervariable region (NP-HVR) decreases. Thus, it becomes increasingly difficult to determine the origin of a virus using only this part of the genome. During outbreaks in Europe and Africa, we found MV strains with identical NP-HVR sequences. However, these strains showed considerable diversity within a larger sequencing window based on concatenated MV phosphoprotein and hemagglutinin genes (P/H pseudogenes). In Belarus, Germany, Russia, and the Democratic Republic of Congo, the P/H pseudogenes provided insights into chains of transmission, whereas identical NP-HVR provided none. In Russia, for instance, the P/H pseudogene identified temporal clusters rather than geographical clusters, demonstrating the circulation and importation of independent variants rather than large local outbreaks lasting for several years, as suggested by NP-HVR. Thus, by extending the sequencing window for molecular epidemiology, a more refined picture of MV circulation was obtained with more clearly defined links between outbreaks and transmission chains. Our results also suggested that in contrast to the P gene, the H gene acquired fixed substitutions that continued to be found in subsequent outbreaks, possibly with consequences for its antigenicity. Thus, a longer sequencing window has true benefits both for the epidemiological surveillance of measles and for the better monitoring of viral evolution.
authors.affiliation: Institute of Immunology, Centre de Recherche Public-Santé/Laboratoire National de Santé, WHO Regional Reference Laboratory for Measles and Rubella and WHO Collaboration Centre for Measles Research, Luxembourg, Luxembourg.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Kessler
authors.forename: Jacques R
authors.initials: JR
authors.lastname: Kremer
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Shulga
authors.forename: Nina T
authors.initials: NT
authors.lastname: Tikhonova
authors.forename: Sabine
authors.initials: S
authors.lastname: Santibanez
authors.forename: Annette
authors.initials: A
authors.lastname: Mankertz
authors.forename: Galina V
authors.initials: GV
authors.lastname: Semeiko
authors.forename: Elena O
authors.initials: EO
authors.lastname: Samoilovich
authors.forename: Jean-Jacques Muyembe
authors.initials: JJ
authors.lastname: Tamfum
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pukuta
authors.forename: Claude P
authors.initials: CP
authors.lastname: Muller
mesh_terms: D000349:Africa / Q000453:epidemiology; D016000:Cluster Analysis; D004196:Disease Outbreaks; D005060:Europe / Q000453:epidemiology; D006389:Hemagglutinins, Viral / Q000235:genetics*; D006801:Humans; D008457:Measles / Q000453:epidemiology* / Q000635:transmission* / Q000821:virology; D008459:Measles virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D058889:Molecular Typing; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D006389:Hemagglutinins, Viral; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D014764:Viral Proteins; C032397:hemagglutinin protein G, measles virus; C058314:nucleoprotein, Measles virus