Harnessing host-virus evolution in antiviral therapy and immunotherapy

Abstract

Pathogen resistance and development costs are major challenges in current approaches to antiviral therapy. The high error rate of RNA synthesis and reverse-transcription confers genome plasticity, enabling the remarkable adaptability of RNA viruses to antiviral intervention. However, this property is coupled to fundamental constraints including limits on the size of information available to manipulate complex hosts into supporting viral replication. Accordingly, RNA viruses employ various means to extract maximum utility from their informationally limited genomes that, correspondingly, may be leveraged for effective host-oriented therapies. Host-oriented approaches are becoming increasingly feasible because of increased availability of bioactive compounds and recent advances in immunotherapy and precision medicine, particularly genome editing, targeted delivery methods and RNAi. In turn, one driving force behind these innovations is the increasingly detailed understanding of evolutionarily diverse host-virus interactions, which is the key concern of an emerging field, neo-virology. This review examines biotechnological solutions to disease and other sustainability issues of our time that leverage the properties of RNA and DNA viruses as developed through co-evolution with their hosts.

Keywords: RNAi; antiviral; host‐oriented; host–virus interaction; information economy paradox; interferon; multifunctional host protein; neo‐virology; vaccine.

Figure 1

Genome and proteome size distribution of RNA versus DNA viruses. Data compiled using the NCBI Viral Genomes Resource,116 taxonomic ID 10239, accessed March 2019. Incomplete, unclassified and sub‐viral genomes excluded. (a) Histogram of virus genome sizes. Orange = RNA viruses; blue = DNA viruses; dashed line = single‐stranded genomes; solid line = double‐stranded genomes. (b) Range and average genome and proteome sizes of viruses plotted in a.

Figure 2

Interaction map of the 10 most multifunctional human proteins targeted most frequently by viruses. The 282 most multifunctional human proteins117 were used to interrogate available protein interaction data with the VirHostNet tool.118 Top 10 virus‐interacting multifunctional host proteins represented in black filled circles and labelled in bold type. Black lines depict host–host protein interactions, and red lines depict host–virus protein interactions. ssRNA viral protein interacting partners represented as coloured filled circles (clockwise from the top: yellow = Flaviviridae, purple = Orthomyxoviridae; light blue = Coronaviridae; dark blue = Togaviridae; grey = Retroviridae; dark green = Filoviridae; red = Pneumoviridae; light green = Arenaviridae; teal = Peribunyaviridae; orange = Phenuiviridae; white = Paramyxoviridae). The complete data set is shown in Supplementary table 1.