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USAMRIID-led Study Tracks Genomic Changes in Ebola Virus in Recent History

NEW YORK (GenomeWeb) – In a study appearing online today in mBio, researchers from the US Army Medical Research Institute of Infectious Diseases (USAMRIID) and elsewhere described mutations and genomic drift patterns detected in Ebola virus isolates collected over four decades.

Using genome sequences from Ebola viruses collected during outbreaks that occurred in the 1970s, 1990s, and present, the team tracked down several hundred SNPs in the Ebola genome — including mutations that could conceivably alter the effectiveness of treatments developed to target given Ebola virus sequences.

"We wanted to highlight an area where genomic drift, the natural process of evolution on this RNA virus genome, could affect the development of therapeutic countermeasures," Gustavo Palacios, senior author of the study and director of USAMRIID's Center for Genome Sciences, said in a statement.

The ongoing outbreak of Ebola virus in West Africa involves a strain known as EBOV/Mak, which began to flare up in the region at the end of 2013, the researchers explained. The scale of the outbreak has prompted renewed interest in finding effective ways to prevent and treat the disease, they noted.

For instance, several sequence-based treatments are under investigation for those already exposed to the Ebola virus, including antibody-, small interfering RNA-, and phosphorodiamidate morpholino oligomer (PMO)-based therapies.

In an effort to understand how isolates circulating today compare with those collected in the past, the team compared genome sequences from the current outbreak with sequences from Ebola strains known as EBOV/Yam-May and EBOV/Kik-9510621, which were implicated in outbreaks in Zaire (currently known as the Democratic Republic of the Congo) in 1976 and 1995, respectively.

Using publicly available genome sequence data for 102 EBOV/Mak isolates collected in West Africa during 2013 and 2014, together with sequence data from EBOV/Yam-May and EBOV/Kik-9510621 strains, the researchers unearthed SNP differences at 640 sites in the Ebola virus genome, providing a peek at the evolutionary drift that has occurred in the virus over the past few decades.

These included mutations involving at least 10 sites that are predicted to impact activity of sequence-based therapeutics by altering monoclonal antibody binding sites, treatment-related siRNA target sites, and so on.

"The virus has not only changed since these therapies were designed, but it's continuing to change," lead author Jeffrey Kugelman, a viral geneticist at USAMRIID and captain with the US Army, said in a statement. "Ebola researchers need to assess drug efficacy in a timely manner to make sure that valuable resources are not spent developing therapies that no longer work."

To that end, Kugelman is reportedly collaborating with researchers and local government officials in Liberia to establish sequencing strategies that would make it possible to rapidly characterize Ebola genomes from patient samples, while coming up with key sequences for diagnosing infection, targeting treatment, and tracking the virus' transmission and mutation patterns during a given outbreak.

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