TY - JOUR
T1 - Host response dynamics following lethal infection of rhesus macaques with zaire ebolavirus
AU - Ebihara, Hideki
AU - Rockx, Barry
AU - Marzi, Andrea
AU - Feldmann, Friederike
AU - Haddock, Elaine
AU - Brining, Douglas
AU - Lacasse, Rachel A.
AU - Gardner, Don
AU - Feldmann, Heinz
N1 - Funding Information:
This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH).
PY - 2011/11/1
Y1 - 2011/11/1
N2 - To gain further insight into the interdependent pathogenic processes in Ebola hemorrhagic fever (EHF), we have examined the dynamics of host responses in individual rhesus macaques infected with Zaire ebolavirus over the entire disease course. Examination of coagulation parameters revealed that decreased coagulation inhibitor activity triggered severe coagulopathy as indicated by prolonged coagulation times and decreased fibrinogen levels. This has been proposed as one of the significant mechanisms underlying disseminated intravascular coagulation in EHF patients. Furthermore, monitoring of expression levels for cytokines/chemokines suggested a mixed anti-inflammatory response syndrome (MARS), which indicates that a catastrophic uncontrolled immunological status contributes to the development of fatal hemorrhagic fever. These results highlight the pathological analogies between EHF and severe sepsis and not only contribute to our understanding of the pathogenic process, but will also help to establish novel postexposure treatment modalities.
AB - To gain further insight into the interdependent pathogenic processes in Ebola hemorrhagic fever (EHF), we have examined the dynamics of host responses in individual rhesus macaques infected with Zaire ebolavirus over the entire disease course. Examination of coagulation parameters revealed that decreased coagulation inhibitor activity triggered severe coagulopathy as indicated by prolonged coagulation times and decreased fibrinogen levels. This has been proposed as one of the significant mechanisms underlying disseminated intravascular coagulation in EHF patients. Furthermore, monitoring of expression levels for cytokines/chemokines suggested a mixed anti-inflammatory response syndrome (MARS), which indicates that a catastrophic uncontrolled immunological status contributes to the development of fatal hemorrhagic fever. These results highlight the pathological analogies between EHF and severe sepsis and not only contribute to our understanding of the pathogenic process, but will also help to establish novel postexposure treatment modalities.
UR - http://www.scopus.com/inward/record.url?scp=80054770588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054770588&partnerID=8YFLogxK
U2 - 10.1093/infdis/jir336
DO - 10.1093/infdis/jir336
M3 - Article
C2 - 21987781
AN - SCOPUS:80054770588
SN - 0022-1899
VL - 204
SP - S991-S999
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - SUPPL. 3
ER -