Interaction of the innate immune system with positive-strand RNA virus replication organelles

Abstract

The potential health risks associated with (re-)emerging positive-strand RNA (+RNA) viruses emphasizes the need for understanding host-pathogen interactions for these viruses. The innate immune system forms the first line of defense against pathogenic organisms like these and is responsible for detecting pathogen-associated molecular patterns (PAMPs). Viral RNA is a potent inducer of antiviral innate immune signaling, provoking an antiviral state by directing expression of interferons (IFNs) and pro-inflammatory cytokines. However, +RNA viruses developed various methods to avoid detection and downstream signaling, including isolation of viral RNA replication in membranous viral replication organelles (ROs). These structures therefore play a central role in infection, and consequently, loss of RO integrity might simultaneously result in impaired viral replication and enhanced antiviral signaling. This review summarizes the first indications that the innate immune system indeed has tools to disrupt viral ROs and other non- or aberrant-self membrane structures, and may do this by marking these membranes with proteins such as microtubule-associated protein 1A/1B-light chain 3 (LC3) and ubiquitin, resulting in the recruitment of IFN-inducible GTPases. Further studies should evaluate whether this process forms a general effector mechanism in +RNA virus infection, thereby creating the opportunity for development of novel antiviral therapies.

Innate Immune Evasion by Human Respiratory RNA Viruses

“…However, it is not yet clear which type I IFN-inducible factors are responsible. Some recent reports (reviewed in [45][46][47]) suggest that intracellular membrane modifications such as viral ROs can be recognized and targeted by guanylate-binding proteins (GBPs), a family of dynamin-related large GTPases, of which DOI: 10.1159/000503030…”

Demarcation of Viral Shelters Results in Destruction by Membranolytic GTPases: Antiviral Function of Autophagy Proteins and Interferon‐Inducible GTPases

“…Often visualized as vacuole‐like membrane compartments (Figure ), the formation and maintenance of the RC is an essential part of the (+)RNA virus life cycle by increasing replication efficiency and avoiding innate recognition . Despite its importance, it was largely unknown whether an antiviral response against the RC exists . Given the structural conservation of RCs across (+)RNA viruses, the RC represents an attractive target for a general antiviral strategy.…”

“…[2,3,[14][15][16] Despite its importance, it was largely unknown whether an antiviral response against the RC exists. [17,18] Given the structural conservation of RCs across (þ)RNA viruses, the RC represents an attractive target for a general antiviral strategy.…”

Chandipura virus requires pro-survival RelA NF-κB function for its propagation

“…Mammalian cells engage innate immune pathways for limiting cytoplasmic RNA virus infections (see Figure 1A). Previous biochemical studies involving vesicular stomatitis virus (VSV) and other prototype RNA viruses defined broadly the biochemical mechanism underlying antiviral host responses (Gerlier and Lyles, 2011;Scutigliani and Kikkert, 2017).…”