Interaction of Viral Capsid-Derived Virus-Like Particles (VLPs) with the Innate Immune System

Abstract

Virus-like particles (VLPs) derived from viral nucleocapsids are an important class of nanoparticles. The structure, uniformity, stability, and function of these VLPs have attracted scientists in utilizing them as a unique tool in various applications in biomedical fields. Their interaction with the innate immune system is of major importance for the adaptive immune response they induce. The innate immune cells and molecules recognize and interact with VLPs on the basis of two major characteristics: size and surface geometry. This review discusses the interaction of viral capsid-derived VLPs with the innate immune system.

Keywords: Toll-like receptor (TLR); adaptive immune system; innate immune system; virus-like particle (VLP).

Figure 1

A schematic diagram of nucleocapsid-derived VLPs illustrating some modifications that can enhance their immunogenicity. (1) packaging of nucleic acids and (2) displaying heterologous proteins/epitopes or functional molecules on the outer surface.

Figure 2

Distribution of VLPs in the draining LN. VLPs arrive in the LNs by natural drainage in a cell-free manner or transported by APCs. Upon reaching the sub-capsular sinus of the draining LN, VLPs will be phagocytized by different APCs and preferentially reach the B and/or T-cell zones. VLPs endocytosed in the periphery by APCs preferentially reach the T-cell zone in the draining LN for T-cell priming.

Figure 3

VLPs and innate humoral immune response. The repetitive surface of viral capsid-derived VLPs facilitates their interaction with molecules and components of the innate humoral immune system. (A) IgM binds the surface of VLPs via low affinity/high avidity interaction. This binding activates C1q molecules resulting in the initiation of the classical complement cascade. (B) More speculative, pentraxin protein family members including CRP, amyloid P SAP and PTX3 may also recognize and bind the repetitive surface structure of VLPs resulting in the activation of C1q molecule and the initiation of the classical complement cascade.

Figure 4

Packaging VLPs with innate immune-modulators. Viral capsid-derived VLPs packaging different nucleic acids can be efficiently internalized by APCs. The packaged nucleic acids will be released in the endosomal compartment of the cell following degradation of VLP-protein shell. ssRNA is TLR7/8 ligand, CpGs is TLR9 ligand and dsRNA is TLR3 ligand. Ligand induced TLR-dimerization activates transcription factors such as NF-κB, AP-1, and IRFs and induces the expression of inflammatory genes and type-I IFN genes.