Science: Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance

[tetano]

Science DOI: 10.1126/science.1259595

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Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance

Angela L. Rasmussen*,1,
Atsushi Okumura*,1,4,
Martin T. Ferris2,
Richard Green1,
Friederike Feldmann3,
Sara M. Kelly1,
Dana P. Scott3,
David Safronetz4,
Elaine Haddock4,
Rachel LaCasse3,
Matthew J. Thomas1,
Pavel Sova1,
Victoria S. Carter1,
Jeffrey M. Weiss1,
Darla R. Miller2,
Ginger D. Shaw2,
Marcus J. Korth1,
Mark T. Heise2,5,
Ralph S. Baric5,
Fernando Pardo Manuel de Villena2,
Heinz Feldmann4,
Michael G. Katze1,?

1Department of Microbiology, University of Washington, Seattle, WA, USA.
2Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
3Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA.
4Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA.
5Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.

↵?Corresponding author. E-mail: honey{at}uw.edu.

↵* These authors contributed equally to this work.

Abstract

Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular coagulation, nor death from shock, thus restricting pathogenesis studies to non-human primates. Here we show that mice from the Collaborative Cross exhibit distinct disease phenotypes following mouse-adapted Ebola virus infection. Phenotypes range from complete resistance to lethal disease to severe hemorrhagic fever characterized by prolonged coagulation times and 100% mortality. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, likely mediated by the susceptibility allele Tek. These data indicate that genetic background determines susceptibility to Ebola hemorrhagic fever.



full article

http://www.sciencemag.org/content/early/2014/10/29/science.1259595.full

 

[gsgs]

Re: Sciene: Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance

Re: Sciene: Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance

9pages .pdf: http://www.sciencemag.org/content/early/2014/10/29/science.1259595.full.pdf



I just saw this on another forum:

http://www.telegraph.co.uk/news/worldnews/ebola/11199589/Ebola-outbreak-Ebola-may-not-be-a-deadly-disease-for-everyone-scientists-find.html

"Ebola virus: Genes 'play significant role in survival'
http://www.bbc.com/news/health-29834687



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The frequency of different pathological manifestations across the 47
CC-RIX lines screened so far are similar in variety and proportion to the
spectrum of clinical disease observed in patients with Ebola virus dis-
ease in the 2014 West Africa outbreak, with hemorrhagic symptoms
appearing in 30-50% of patients (27, 28). Although we cannot rule out
the possibility that human survivors have pre-existing immunity to
EBOV or a related virus, our data suggest that genetic factors play a
significant role in determining disease outcome in naïve individuals
without prior exposure or immunologic priming.

 

[Emily]

Re: Science: Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance

Prof Andrew Easton, Professor of Virology, University of Warwick, said:?This paper demonstrates that the genes of the host play a role in determining the outcome of Ebola infection in terms of the severity of the disease, at least in mice.

Highly inbred mice infected with MA-EBOV. a lab-created strain since 'natural' strains that infect humans won't sicken mice.