Interferon in rabies virus infection

Abstract

Rabies is among the longest known and most dangerous and feared infectious diseases for humans and animals and still is responsible for tenth of thousands of human deaths per year. The rabies virus (RABV) is a rather atypical member of the Rhabdoviridae family as it has completely adapted during evolution to warm-blooded hosts and is directly transmitted between them, whereas most other rhabdoviruses are transmitted by insect vectors. The virus is also unique with respect to its extremely broad host species range and a very narrow host organ range, namely its strict neurotropism. It is becoming increasingly clear that the host innate immune system, particularly the type I interferon system, and the viral counteractions profoundly shape this virus-host relationship. In the past few years, exciting new insight was obtained on how viruses are sensed by innate immune receptors, how the downstream signaling networks for activation of interferon are working, and how viruses can interfere with the system. While RABV 5'-triphosphate RNAs were identified as the major pathogen-associated molecular pattern sensed by cytoplasmic RIG-I-like receptors (RLR), the RABV phosphoprotein (P) has emerged as a potent multifunctional antagonist able to counteract the signaling cascades leading to transcriptional activation of interferon genes as well as interferon signaling pathways, thereby limiting expression of antiviral and immune-stimulatory genes.