Abstract
BackgroundBats 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).ResultsThe 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-014-0532-x) contains supplementary material, which is available to authorized users.
Highlights
Bats are a major reservoir of emerging infectious viruses
To circumvent the reliance on high-quality annotation models, we recently developed proteomics informed by transcriptomics (PIT) analysis
Hendra virus (HeV) up-regulates pro-apoptotic pathways in PaKiT03 cells Considering the enrichment of apoptosis-related genes within the PaKiT03 cells, we examined if the expression of transcripts and proteins involved in the apoptotic response differed between the cell lines
Summary
Bats are a major reservoir of emerging infectious viruses Many of these viruses are highly pathogenic to humans bats remain asymptomatic. 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). Despite the fact that many of the zoonotic viruses harbored by bats are highly pathogenic to their spillover hosts, bats remain clinically unaffected and rarely display any signs of disease. Despite the absence of clinical disease, bats are capable of shedding virus and triggering subsequent zoonotic transmission. This situation implies bats are capable of controlling viral replication, but not eliminating it. Zoonotic transmission of HeV to horses and humans is often fatal [15]
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