Proteomics informed by transcriptomics reveals  Hendra virus sensitizes bat cells to TRAIL-mediated  apoptosis.
BACKGROUND
Bats are a major reservoir of emerging infectious viruses. Many of these viruses are highly pathogenic to humans however bats remain asymptomatic. The mechanism by which bats control viral replication is unknown. Here we utilize an integrated approach of proteomics informed by transcriptomics to compare the response of immortalized bat and human cells following infection with the highly pathogenic bat-borne Hendra virus (HeV).


RESULTS
The host response between the cell lines was significantly different at both the mRNA and protein levels. Human cells demonstrated minimal response eight hours post infection, followed by a global suppression of mRNA and protein abundance. Bat cells demonstrated a robust immune response eight hours post infection, which led to the up-regulation of apoptosis pathways, mediated through the tumor necrosis factor-related apoptosis inducing ligand (TRAIL). HeV sensitized bat cells to TRAIL-mediated apoptosis, by up-regulating death receptor transcripts. At 48 and 72 hours post infection, bat cells demonstrated a significant increase in apoptotic cell death.


CONCLUSIONS
This is the first study to comprehensively compare the response of bat and human cells to a highly pathogenic zoonotic virus. An early induction of innate immune processes followed by apoptosis of virally infected bat cells highlights the possible involvement of programmed cell death in the host response. Our study shows for the first time a side-by-side high-throughput analysis of a dangerous zoonotic virus in cell lines derived from humans and the natural bat host. This enables a way to search for divergent mechanisms at a molecular level that may influence host pathogenesis.
James W
JW
Wynne
Brian J
BJ
Shiell
Glenn A
GA
Marsh
Victoria
V
Boyd
Jennifer A
JA
Harper
Kate
K
Heesom
Paul
P
Monaghan
Peng
P
Zhou
Jean
J
Payne
Reuben
R
Klein
Shawn
S
Todd
Lawrence
L
Mok
Diane
D
Green
John
J
Bingham
Mary
M
Tachedjian
Michelle L
ML
Baker
David
D
Matthews
Lin-Fa
LF
Wang
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002685:Chiroptera / Q000235:genetics / Q000821:virology; D045404:Hendra Virus / Q000235:genetics* / Q000472:pathogenicity; D045464:Henipavirus Infections / Q000235:genetics* / Q000635:transmission / Q000821:virology; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D040901:Proteomics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
D053221:TNF-Related Apoptosis-Inducing Ligand