ena-STUDY-BRISTOL-29-09-2014-15:10:58:351-538
Ebola virus (EBOV) was passaged repeatedly in guinea pigs until it become highly pathogenic. At each stage the RNA from spleen samples was sequenced and the viral sequences mapped to the EBOV genome
Background. Ebola virus causes a severe and often fatal hemorrhagic fever in humans, with some strains such as Ebola virus Zaire have case fatality rates approaching 90%.  Currently the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa and has spread from Guinea to Liberia, Sierra Leone and Nigeria.  Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted to infecting humans. Results.  To investigate whether Ebola virus can undergo genetic changes in response to adaptation in a different host, a Guinea pig model of infection was used.  In this experimental system, Guinea pigs were infected with Ebola virus Zaire, which initially did not cause disease.  To simulate transmission to uninfected individuals the virus was serially passaged five times in naive animals.  As the virus was passaged, virulence increased and clinical effect on the Guinea pig.  An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage. Conclusions.  Upon passage in the Guinea pig model, Ebola virus Zaire became more virulent, certain amino acid substitutions and genome editing became established that led to amino acid coding changes, and these may be associated with virulence.
Background. Ebola virus causes a severe and often fatal hemorrhagic fever in humans, with some strains such as Ebola virus Zaire have case fatality rates approaching 90%.  Currently the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa and has spread from Guinea to Liberia, Sierra Leone and Nigeria.  Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted to infecting humans. Results.  To investigate whether Ebola virus can undergo genetic changes in response to adaptation in a different host, a Guinea pig model of infection was used.  In this experimental system, Guinea pigs were infected with Ebola virus Zaire, which initially did not cause disease.  To simulate transmission to uninfected individuals the virus was serially passaged five times in naive animals.  As the virus was passaged, virulence increased and clinical effect on the Guinea pig.  An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage. Conclusions.  Upon passage in the Guinea pig model, Ebola virus Zaire became more virulent, certain amino acid substitutions and genome editing became established that led to amino acid coding changes, and these may be associated with virulence.