Pestiviral E-rns blocks TLR-3-dependent IFN synthesis by LL37 complexed RNA

作者：Zuercher Christoph; Sauter Kay Sara; Schweizer Matthias^*

来源：Veterinary Microbiology, 2014, 174(3-4): 399-408.

DOI：10.1016/j.vetmic.2014.09.028

• Bovine viral diarrhea virus (BVDV)
• Interferon (IFN)
• Viral endoribonuclease
• Secondary structure
• Human cathelicidin LL37
• TLR-3

The ribonuclease activity of the soluble glycoprotein E-rns of pestiviruses represents a unique mechanism to circumvent the host%26apos;s innate immune system by blocking interferon type-I synthesis in response to extracellularly added single- (ss) and double-stranded (ds) RNA. However, the reason why pestiviruses encode a ribonuclease in addition to the abundant serum RNases remained elusive. Here, we show that the 5%26apos; UTR and NS5B regions of various strains of the RNA genome of the pestivirus bovine viral diarrhea virus (BVDV) are resistant to serum RNases and are potent TLR-3 agonists. Inhibitory activity of E-rns was restricted to cleavable RNA products, and did not extend to the synthetic TLR-7/8 agonist R-848. RNA complexed with the antimicrobial peptide LL37 was protected from degradation by Ems in vitro but was fully inhibited by E-rns in its ability to induce IFN in cell cultures, suggesting that the viral protein is mainly active in cleaving RNA in an intracellular compartment. We propose that secreted E-rns represents a potent IFN antagonist, which degrades viral RNA that is resistant to the ubiquitous host RNases in the extracellular space. Thus, the viral RNase prevents its own pathogen-associated molecular pattern (PAMP) to inadvertently activate the IFN response that might break innate immunotolerance required for persistent pestivirus infections.

• 出版日期2014-12-5