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Ebola Re-emergence in Liberia Involved Virus With Reduced Evolutionary Rate, Study Suggests

NEW YORK (GenomeWeb) – The mutational rate appears to have waned slightly in Ebola viruses that re-emerged in Liberia after that country's main outbreak subsided, according to a study published today in Science Advances.

Researchers from the US Centers for Disease Control and Protection, the US Army Medical Research Institute of Infectious Diseases, Liberia's Ministry of Health, and elsewhere analyzed genomic and epidemiologic data from seven individuals with confirmed Ebola infections to investigate an Ebola virus flare up in Liberia in June 2015 — the second re-emergence of the virus after the broader Ebola outbreak ended in that country.

Compared with Ebola viruses profiled previously, the team saw declining genetic divergence in the flare-up strains, perhaps due to diminished evolutionary rates in individuals with persistent infection. Still, the sequence data supported the notion that the flare-ups involved strains related to those in the main outbreak, ruling out re-introduction from a reservoir animal or transmission of distinct strains from active infections elsewhere.

"[T]his second flare-up, like the first, originated from a persistently infected source within Liberia," co-senior authors USAMRIID’s Gustavo Palacios, the CDC's Athalia Christie, and Ministry of Health researcher Tolbert Nyenswah, and their colleagues wrote. They also noted that the new Ebola genomes "were characterized by significantly low levels of genetic divergence compared to other viral genomes sequenced from samples collected from infected persons in Liberia during the epidemic."

The findings highlight the potential risk of re-introduction due to Ebola virus persistence in some individuals who survived the disease, highlighting the importance of enhanced surveillance, survivor services, and access to resources for responding to flare-ups, Christie, Ebola response lead for CDC in Liberia, told GenomeWeb in an e-mail.

Members of the same team published a paper in Cell Host & Microbe late last year that used genome sequences for hundreds of Ebola isolates to assess the second wave of Liberia's Ebola outbreak, which began in May 2014.

Authors of that study and others since have encouraged ongoing Ebola surveillance in West Africa, particularly in light of research suggesting the virus can persist in semen and be sexually-transmitted by symptom-free survivors.

One of those cases was linked to a flare-up in Liberia in March 2015, the first of several in the country. Another Ebola resurgence with seven confirmed cases was documented in Liberia from late last June until mid-July, followed by a flare-up starting in November 2015, involving at least three cases in Liberia. For their current analysis, the researchers focused on the seven cases documented during the second re-emergence.

The flare-up was first detected through a positive quantitative RT-PCR-based test for Ebola RNA in an oral swab from a 17-year-old boy who had died in a Liberian village called Needowein. In the weeks that followed, half a dozen more individuals tested positive for Ebola by qRT-PCR, while another case was not conclusively confirmed.

Using blood or oral swab samples from five of the individuals infected in Needowein, collaborators at the LIBR Genome Center used the Illumina MiSeq to generate eight Ebola genomes.

A phylogenetic analysis of the genomes and sequences from other West African Ebola virus isolates suggest the flare-up strains are closely related to the Ebola virus sub-lineage LB2, which was circulating in Liberia previously, but not widely distributed in Guinea and Sierra Leone, the researchers reported.

The newly sequenced genomes were nearly identical to one another, all containing several substitutions compared to strains profiled in the broader West African outbreak as well as new substitutions specific to the flare-up isolates. These and other findings from the analyses pointed to "a reduced rate [Ebola virus] evolution during persistent infections," the authors wrote, noting that virus' evolutionary rate also dipped in the March 2015 flare-up involving sexual transmission of the Ebola virus.

Based on the genetic and epidemiological data available, they suspect that the virus that re-emerged in June 2015 was linked to cases from a neighboring community called Barclay Farm the previous fall.

The team has reportedly gone on to sequence samples from the November flare-up in Liberia in an effort to continue untangling potential routes of Ebola virus re-emergence.

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