Antivirotics based on defective interfering particles: emerging concepts and challenges

Figures

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  Figure 1. General principles of DIPs biology and resulting DIP/STV ratios in the cell culture. DIPs have a truncated genome and the gene responsible for replication is damaged. When infected with DIPs only, the cell does not generate any more viral particles. In case of coinfection with DIPs and STV, both viral particles proliferate in the cell, competing for resources in the process. When infected with STV only, mistakes in the replication process lead to formation of different DIPs. “-” indicates the absence of STV or DIPs production. “+” indicates the intensity of STV or DIPs production.

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  Figure 2. High-yield approaches to DIPs production. STV-dependent approaches require the presence of active original virus and therefore cannot be considered biologically safe. STV-independent approach illustrates the method proposed by Najat Bdeir et al. (2019). In this approach, DI-244 particles of IAV were generated solely from the plasmids, using 293T and MDCK cell lines, stably expressing codon optimized PB2; GM = genetically modified.

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  Figure 3. Stages of viral infection and competition resources between STV and DIP. During coinfection, STV and DIPs compete for distinct cellular/viral resources at every stage of the infection. In this way DIPs limit reproduction and expansion of STV.

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  Figure 4. Mechanisms of DIPs production in vitro (A) and their therapeutic effect (B).