Genomic Differences between Guinea Pig Lethal and Nonlethal Marburg Virus Variants

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 190% 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.Marburg viruses (MARVs) and the related Ebola viruses (EBOVs) comprise the family Filoviridae; together with the Bornaviridae, Paramyxoviridae, and Rhadboviridae, they constitute the order Mononegavirales.The known etiological agents of Marburg hemorrhagic fever include the following MARV strains (genus Marburgvirus, species Lake Victoria marburgvirus): Angola2005 (Ang), Ci67, 05DRC (Democratic Republic of the Congo), 07DRC, 09DRC, Musoke (Mus), Ozolin (Ozo), Popp (Pop), and Ravn (Rav) [1].Most filoviruses cause severe hemorrhagic fever with high mortality rates among humans and nonhuman primates, without prior adapta-Potential conflicts of interest: none reported.