Thursday, August 28, 2014

Study: Ebola Virus Is Rapidly Evolving




# 9015


One of the concerns we have when any zoonotic virus spills over into the human population is that over time, as it passes from one person to the next, it could pick up host adaptations – mutations – that could make the virus a greater threat over time.


In the laboratory, researchers will often conduct serial passage experiments (see Serial Passage Of H5N2 In Mice) to observe these evolutionary changes, and try to figure out what they mean.


Often, these genetic changes are of little or no effect, and can sometimes even be detrimental to the `biological fitness’ of the virus. Those that favor replication in the new found host, however, tend to carry on to produce more progeny, advancing their new lineage forward,  drowning out the earlier `wild type’ virus in the host.


A recent concern has been that Ebola - which up until now has never really spread in kind of long chains of human cases that we are seeing now – could better adapt to human physiology over time.


Today we’ve a study appearing in the Journal Science where scientists sequenced 99 Ebola viruses taken from 78 people from Sierra Leone during the month of June, and found that the virus is showing a marked propensity to accumulate `interhost and intrahost genetic variation’ as it passages through the population.


First a bit from the study, then I’ll be back with more.

Published Online August 28 2014

Science DOI: 10.1126/science.1259657

Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

Stephen K. Gire1,2,*, Augustine Goba3,*,†, Kristian G. Andersen1,2,*,†, Rachel S. G. Sealfon2,4,*, Daniel J. Park2,*, Lansana Kanneh3, Simbirie Jalloh3, Mambu Momoh3,5, Mohamed Fullah3,5,‡, Gytis Dudas6, Shirlee Wohl1,2,7, Lina M. Moses8, Nathan L. Yozwiak1,2, Sarah Winnicki1,2, Christian B. Matranga2, Christine M. Malboeuf2, James Qu2, Adrianne D. Gladden2, Stephen F. Schaffner1,2, Xiao Yang2, Pan-Pan Jiang1,2, Mahan Nekoui1,2, Andres Colubri1, Moinya Ruth Coomber3, Mbalu Fonnie3,‡, Alex Moigboi3,‡, Michael Gbakie3, Fatima K. Kamara3, Veronica Tucker3, Edwin Konuwa3, Sidiki Saffa3, Josephine Sellu3, Abdul Azziz Jalloh3, Alice Kovoma3,‡, James Koninga3, Ibrahim Mustapha3, Kandeh Kargbo3, Momoh Foday3, Mohamed Yillah3, Franklyn Kanneh3, Willie Robert3, James L. B. Massally3, Sinéad B. Chapman2, James Bochicchio2, Cheryl Murphy2, Chad Nusbaum2, Sarah Young2, Bruce W. Birren2, Donald S. Grant3, John S. Scheiffelin8, Eric S. Lander2,7,9, Christian Happi10, Sahr M. Gevao11, Andreas Gnirke2,§, Andrew Rambaut6,12,13,§, Robert F. Garry8,§, S. Humarr Khan3,‡§, Pardis C. Sabeti1,2,†§


In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2,000x coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from Middle African lineages ~2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Since many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.

These researchers found that the virus had evolved into three distinct lineages in Sierra Leone during the month of June (one of which appears to have died out), along with accumulating scores of amino acid changes to its genome.


It should be noted that while scientists have the ability to sequence and compare these variant viruses, they don’t necessarily know what these individual mutations (or their aggregate) means to the virus, or how it might change its behavior. 


Based on the location of some these changes, there are concerns that the PCR primers currently used to detect it patients may need adjusting, and that some of the antiviral drugs being developed could be impacted as well. 


And while it is theoretically possible that changes to the genome could affect the transmissibility of the virus, we haven’t seen any evidence of that happening.


Unknown at this time are what genetic changes might be occurring in the virus in Liberia and Guinea, or even Nigeria. The bottom line, however, is that the longer this virus circulates in humans, the better chance it has of producing a mutation we really don’t want to see.


For some more coverage on this report, NPR’s Goats & Soda Blog has:


Ebola Is Rapidly Mutating As It Spreads Across West Africa

by Michaeleen Doucleff



This from Scientific American:


Patient Zero Believed to be Sole Source of Ebola Outbreak

By pinpointing the virus’s source, a new report validates steps health care workers are taking to battle the disease

Aug 28, 2014 |By Dina Fine Maron

And this from Nature News. 


Ebola virus mutating rapidly as it spreads

Outbreak likely originated with a single animal-to-human transmission.

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