Signaling through RIG-I and type I interferon receptor: Immune activation by Newcastle disease virus in man versus immune evasion by Ebola virus (Review)

Abstract

In this review, two types of RNA viruses are compared with regard to the type I interferon (IFN) response in order to obtain a better understanding of the molecular mechanisms of immune activation or evasion. Upon human infection, both viruses exert either beneficial or detrimental effects. The Newcastle disease virus (NDV), is a type strain for avian paramyxoviruses, while the Ebola virus (EBOV), is a virus affecting primates. During evolution, both viruses specifically adapted to their respective hosts, acquiring sophisticated viral escape mechanisms. Two types of receptors play an important role in the life cycle of these two viruses: cytoplasmic retinoic acid‑inducible gene I (RIG‑I) and membrane expressed type I IFN receptor (IFNAR). In mouse and human cells, NDV is a strong inducer of the type I IFN response. The early phase of this is initiated by signaling through RIG‑I and the late response by signaling through IFNAR. EBOV does not induce type I IFN responses in humans as it has viral proteins that specifically and strongly interfere with RIG‑I and IFNAR signaling, as well as immune activation. In this review, we discuss whether the beneficial effects of one virus can be exploited in the fight against the detrimental effects of the other.

Genetic variants in IFIH1 and DDX58 influence hepatitis C virus clearance in Chinese Han population

“…IFIH1 could induce IFN‐α/β and interferon‐inducible genes to regulate the production of type I IFN and various proinflammatory cytokines by activating transcription factors such as IRF‐3, IRF7, and NF‐κB . Type I INFs further stimulating dendritic cells, and natural killers, thereby exerting antiviral effects by promoting the effector functions of B and T cells .…”

Robust Lys63-Linked Ubiquitination of RIG-I Promotes Cytokine Eruption in Early Influenza B Virus Infection

“…NDV infection causes the activation of multiple transcription factors and induces robust type I IFN expression at an early phase of infection dependent on the RIG-I-mediated signaling pathway (48)(49)(50). The immediate genes whose expression is stimulated by SeV infection are mainly dependent on the activation of IRF3 and NF-B (51).…”

Immunobiology of Newcastle Disease Virus and Its Use for Prophylactic Vaccination in Poultry and as Adjuvant for Therapeutic Vaccination in Cancer Patients

“…The studies revealed an important role in the IFN response of RIG-I, IRF3, IFN-β and IRF7 [6,27]. In addition, studies with cells from Knock-out mice devoid of the gene for IFNRA showed the importance of this receptor: In its absence, normal cells were incapable of preventing NDV replication [49,50]. …”

“…Ebola virus (EBOV) from primates has during evolution developed immune escape mechanisms from the type I IFN response of primate cells [50]. EBOV, first discovered in 1976, belongs to the largest known RNA viruses.…”

“…This may be particularly relevant for individuals who come into contact with patients infected for instance with EBOV [50]. A recNDV engineered to express EBOV viral antigens could be well suited as a prophylactic vaccine because it would express HN as adjuvant to stimulate a strong type I interferon response as well as target antigens from EBOV.…”