title: Variation in the glycoprotein and VP35 genes of Marburg virus strains.
abstract: Marburg virus, the prototype of the family Filoviridae, differs genetically, serologically, and morphologically from Ebola viruses. To better define the genetic variation within the species, VP35 and glycoprotein (GP) genes of representative human isolates from four known episodes of Marburg virus hemorrhagic fever were analyzed. The percentage nucleotide differences in the GP gene coding regions of Marburg viruses (0.1-21%) was nearly equal to the percentage amino acid changes (0-23%), while the percentage nucleotide differences in VP35 coding regions (0.3-20.9%) were higher than the percentage amino acid changes (0.9-6.1%), indicating a greater number of nonsynonymous changes occurring in the GP gene. The higher variation in the GP gene and the corresponding protein, especially those changes in the variable middle region of the GP, suggests that the variability may be the result of responses to natural host pressures. Analysis of the GP gene open reading frame shows a nonrandom distribution of nonsynonymous mutations that may indicate positive Darwinian selection is operating within the variable region. A heptad repeat region and an adjoining predicted fusion peptide are found in the C-terminal third of Marburg virus GPs, as has been previously shown for Ebola virus, and are similar to those found in transmembrane glycoproteins of retroviruses, paramyxoviruses, coronaviruses, and influenza viruses. Comparative analyses showed that there are two lineages within the Marburg virus species of filoviruses. The most recent isolate from Kenya (1987) represents a separate genetic lineage within the Marburg virus species (21-23% amino acid difference). However, this lineage likely does not represent a separate Marburg subtype, as the extent of divergence is less than that separating Ebola virus subtypes.
authors.affiliation: Special Pathogens Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. ans1@cdc.gov
authors.forename: A
authors.initials: A
authors.lastname: Sanchez
authors.forename: S G
authors.initials: SG
authors.lastname: Trappier
authors.forename: U
authors.initials: U
authors.lastname: Ströher
authors.forename: S T
authors.initials: ST
authors.lastname: Nichol
authors.forename: M D
authors.initials: MD
authors.lastname: Bowen
authors.forename: H
authors.initials: H
authors.lastname: Feldmann
mesh_terms: D000595:Amino Acid Sequence; D015023:Democratic Republic of the Congo; D005814:Genes, Viral; D014644:Genetic Variation; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007630:Kenya; D029024:Marburgvirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014454:Uganda; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins; D015678:Viral Structural Proteins / Q000235:genetics*; D015030:Zimbabwe
chemical_list: D006023:Glycoproteins; D012367:RNA, Viral; C080980:VP35 protein, filovirus; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D015678:Viral Structural Proteins