Mechanisms and Consequences of Ebolavirus-Induced Lymphocyte Apoptosis
Abstract
Ebolavirus (EBOV) is a member of the filovirus family and causes severe hemorrhagic fever, resulting in death in up to 90% of infected humans. EBOV infection induces massive bystander lymphocyte apoptosis; however, neither the cellular apoptotic pathway (s) nor the systemic implications of lymphocyte apoptosis in EBOV infection are known. In this study, we show data suggesting that EBOV-induced lymphocyte apoptosis in vivo occurs via both the death receptor (extrinsic) and mitochondrial (intrinsic) pathways as both Fas-associated death domain dominant negative transgenic mice and mice overexpressing bcl-2 were resistant to EBOV-induced lymphocyte apoptosis. Surprisingly, inhibiting lymphocyte apoptosis during EBOV infection did not result in improved animal survival. Furthermore, we show for the first time that hepatocyte apoptosis likely occurs in EBOV infection, and that mice lacking the proapoptotic genes Bim and Bid had reduced hepatocyte apoptosis and liver enzyme levels postinfection. Collectively these data suggest that EBOV induces multiple proapoptotic stimuli and that blocking lymphocyte apoptosis is not sufficient to improve survival in EBOV infection. These data suggest that hepatocyte apoptosis may play a role in the pathogenesis of EBOV infection, whereas lymphocyte apoptosis appears to be nonessential for EBOV disease progression. The Journal of Immunology, 2010, 184: 327-335.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 31, 2011
- Accession Number
- ADA536534
Entities
People
- Eizo Watanabe
- Jonathan E. Mcdunn
- Mark A. Smith
- Paul E. Swanson
- Richard S. Hotchkiss
- Sina Bavari
- Steven B. Bradfute
Organizations
- United States Army Medical Research Institute of Infectious Diseases