Key result
In EV71-infected human intestinal epithelial cells (HT-29), TLR/TRIF signaling remained intact and induced robust antiviral interferon production, whereas TRIF was degraded by viral 3Cpro in other cell types.
Intact TLR/TRIF signaling in human intestinal epithelial cells allows for robust interferon induction against EV71, unlike in other cell types where TRIF is degraded by viral proteases, potentially explaining the lack of gastrointestinal symptoms in EV71 infection.
Answers are grounded in this paper and cite their sources.
May explain absent GI symptoms in EV71; hypothesis-generating for cell-targeted antivirals in humans.
Enterovirus 71 (EV71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. Few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to EV71 in the gut. We reported a robust induction of interferons (IFNs) in human intestinal epithelial cells (HT-29), which was suppressed in other types such as RD and HeLa cells. The underlying mechanism for the apparent difference remains obscure. In this study we report that in EV71-infected HT-29 cells, TLR/TRIF signaling was essential to IFN induction; viral replication increased and the induction of IFN-α, -β, -ω, -κ, and -ε decreased markedly in TRIF-silenced HT-29 cells. Importantly, TRIF was degraded by viral 3Cpro in RD cells, but resisted cleavage, and IRF3 was activated and translocated into the nucleus in HT-29 cells. Taken together, our data suggest that IFNs were induced differentially in human HT-29 cells through an intact TLR/TRIF signaling, which differs from other cell types and may be implicated in viral pathogenesis in EV71 infection.
No takes yet. Share an insight, caveat, or question.
Wang et al. (2016) studied Enterovirus 71 infection. Enterovirus 71 infection vs. Uninfected cells and other cell lines (RD, HeLa) was evaluated on Induction of antiviral interferons and TLR/TRIF signaling activation. In EV71-infected human intestinal epithelial cells (HT-29), TLR/TRIF signaling remained intact and induced robust antiviral interferon production, whereas TRIF was degraded by viral 3Cpro in other cell types.
Synapse has enriched 10 related papers. Consider them for comparative context: