title: Genomic differences between guinea pig lethal and nonlethal Marburg virus variants.
abstract: The complete genome sequences of 2 closely related plaque-derived variants of Marburg virus (MARV) species Lake Victoria marburgvirus, strain Musoke, indicate only a few regions of the RNA genome as underlying the differences between the 2 viruses. One variant is >90% lethal for guinea pigs and the other much less virulent, when guinea pigs are challenged with 1000 pfu of virus. Only 4 mutations that result in amino acid changes were identified, 1 in viral matrix protein VP40 and 3 in L, the RNA-dependent RNA polymerase. In addition, 6 differences were identified in noncoding regions of transcribed mRNA, and 1 silent codon change was identified in the L gene. Interestingly, the amino acid mutation identified in VP40 occurs in a nonconserved loop structure between 2 domains that are homologues only among MARV species. The L gene mutations were equally intriguing, clustering near a highly conserved motif in viral RNA-dependent RNA polymerases.
authors.affiliation: Viral Pathogenesis and Immunology Branch, Virology Division, US Army Medical Research Institute for Infectious Diseases, Frederick, MD 21702, USA. loreen.lofts@us.army.mil
authors.forename: Loreen L
authors.initials: LL
authors.lastname: Lofts
authors.forename: M Sofi
authors.initials: MS
authors.lastname: Ibrahim
authors.forename: Diane L
authors.initials: DL
authors.lastname: Negley
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hevey
authors.forename: Alan L
authors.initials: AL
authors.lastname: Schmaljohn
mesh_terms: D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D004195:Disease Models, Animal; D014644:Genetic Variation; D006168:Guinea Pigs; D008379:Marburg Virus Disease / Q000401:mortality* / Q000503:physiopathology*; D029024:Marburgvirus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D013045:Species Specificity; D010948:Viral Plaque Assay
chemical_list: D018076:DNA, Complementary; D004279:DNA, Viral; D012367:RNA, Viral