Dataset Information

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.

SUBMITTER: Kessler JR

PROVIDER: S-EPMC3043479 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Revealing new measles virus transmission routes by use of sequence analysis of phosphoprotein and hemagglutinin genes.

Kessler Julia R JR Kremer Jacques R JR Shulga Sergey V SV Tikhonova Nina T NT Santibanez Sabine S Mankertz Annette A Semeiko Galina V GV Samoilovich Elena O EO Tamfum Jean-Jacques Muyembe JJ Pukuta Elisabeth E Muller Claude P CP

Journal of clinical microbiology 20101124 2

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 pseudogene ...[more]

PMID: 21106790

Similar Datasets

Project description:UnlabelledThe genome of nonsegmented negative-strand RNA viruses is tightly embedded within a nucleocapsid made of a nucleoprotein (N) homopolymer. To ensure processive RNA synthesis, the viral polymerase L in complex with its cofactor phosphoprotein (P) binds the nucleocapsid that constitutes the functional template. Measles virus P and N interact through two binding sites. While binding of the P amino terminus with the core of N (NCORE) prevents illegitimate encapsidation of cellular RNA, the interaction between their C-terminal domains, P(XD) and N(TAIL) is required for viral RNA synthesis. To investigate the binding dynamics between the two latter domains, the P(XD) F497 residue that makes multiple hydrophobic intramolecular interactions was mutated. Using a quantitative mammalian protein complementation assay and recombinant viruses, we found that an increase in P(XD)-to-N(TAIL) binding strength is associated with a slower transcript accumulation rate and that abolishing the interaction renders the polymerase nonfunctional. The use of a newly developed system allowing conditional expression of wild-type or mutated P genes, revealed that the loss of the P(XD)-N(TAIL) interaction results in reduced transcription by preformed transcriptases, suggesting reduced engagement on the genomic template. These intracellular data indicate that the viral polymerase entry into and progression along its genomic template relies on a protein-protein interaction that serves as a tightly controlled dynamic anchor.ImportanceMononegavirales have a unique machinery to replicate RNA. Processivity of their polymerase is only achieved when the genome template is entirely embedded into a helical homopolymer of nucleoproteins that constitutes the nucleocapsid. The polymerase binds to the nucleocapsid template through the phosphoprotein. How the polymerase complex enters and travels along the nucleocapsid template to ensure uninterrupted synthesis of up to ∼ 6,700-nucleotide messenger RNAs from six to ten consecutive genes is unknown. Using a quantitative protein complementation assay and a biGene-biSilencing system allowing conditional expression of two P genes copies, the role of the P-to-N interaction in polymerase function was further characterized. We report here a dynamic protein anchoring mechanism that differs from all other known polymerases that rely only onto a sustained and direct binding to their nucleic acid template.

Project description:BackgroundA measles outbreak occurred in a western county of China in 2013, the year after China's historic nadir of measles. We conducted a field investigation to identify gaps in measles vaccination coverage and immunization program weaknesses, and to provide recommendations for measles outbreak response and immunization program improvement.MethodsWe analyzed surveillance data from 2008 to 2013 to describe the measles epidemiology of the county. Measles-containing vaccine coverage was estimated using two methods: previously-reported administrative coverage and an estimation of coverage by clinic-kept vaccination records (n = 542). We conducted a rapid field coverage assessment in a migrant population village to evaluate coverage after emergency vaccination. We conducted a review of hospital records of measles cases to address the role hospital transmission played during the early stage of this outbreak.ResultsThere were 153 cases in the outbreak, primarily among children too young to vaccinate, unvaccinated children less than 3 years old, and adults. Measles-containing vaccine coverage by the field assessment showed that 20% of children aged 8-17 months had zero doses, and 9% of ≥2 years old children had fewer than two doses. The vaccination statuses of all adult cases were either zero doses or unknown. At least 61% of cases had been hospitalized. The proportion of cases who had been hospital-exposed 7 to 21 days prior to rash onset decreased from 52% to 22% after hospitals strengthen their isolation measures.ConclusionsThis outbreak was a result of measles vaccination coverage gaps among young children and adults, and insufficient hospital isolation of cases. The lower coverage seen in the field estimation compared with reported coverage showed that reported coverage could have been overestimated. Hospitals were sites of transmission in the early stage of the outbreak. A strict hospital isolation policy could decrease spread of measles. Emergency vaccination was associated with stopping measles transmission in low coverage areas.

Project description:BackgroundChina experienced several large measles outbreaks in the past two decades, and a series of enhanced control measures were implemented to achieve the goal of measles elimination. Molecular epidemiologic surveillance of wild-type measles viruses (MeV) provides valuable information about the viral transmission patterns. Since 1993, virologic surveillnace has confirmed that a single endemic genotype H1 viruses have been predominantly circulating in China. A component of molecular surveillance is to monitor the genetic characteristics of the hemagglutinin (H) gene of MeV, the major target for virus neutralizing antibodies.Principal findingsAnalysis of the sequences of the complete H gene from 56 representative wild-type MeV strains circulating in China during 1993-2009 showed that the H gene sequences were clustered into 2 groups, cluster 1 and cluster 2. Cluster1 strains were the most frequently detected cluster and had a widespread distribution in China after 2000. The predicted amino acid sequences of the H protein were relatively conserved at most of the functionally significant amino acid positions. However, most of the genotype H1 cluster1 viruses had an amino acid substitution (Ser240Asn), which removed a predicted N-linked glycosylation site. In addition, the substitution of Pro397Leu in the hemagglutinin noose epitope (HNE) was identified in 23 of 56 strains. The evolutionary rate of the H gene of the genotype H1 viruses was estimated to be approximately 0.76×10(-3) substitutions per site per year, and the ratio of dN to dS (dN/dS) was <1 indicating the absence of selective pressure.ConclusionsAlthough H genes of the genotype H1 strains were conserved and not subjected to selective pressure, several amino acid substitutions were observed in functionally important positions. Therefore the antigenic and genetic properties of H genes of wild-type MeVs should be monitored as part of routine molecular surveillance for measles in China.

Dataset Information

Revealing new measles virus transmission routes by use of sequence analysis of phosphoprotein and hemagglutinin genes.

Publications

Revealing new measles virus transmission routes by use of sequence analysis of phosphoprotein and hemagglutinin genes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets