Modeling the therapeutic potential of defective interfering particles in the presence of immunity

Defective interfering particles (DIPs) are naturally occurring viruses that have evolved to parasitize other viruses. They suppress wild-type (WT) virus infections through their role as intracellular parasites. Because most encode few or no viral proteins, they have been entertained as possible safe antiviral therapies-something that might be given to patients infected with the WT virus. Adding to their safety, they cannot reproduce except when co-infecting the same cells as the WT, so they pose no danger of evolving into independent disease agents. But this dependence on the WT also limits their therapeutic utility by restricting the timing at which their administration can be effective. To develop a qualitative sense of these constraints for acute viral infections, we use ordinary differential equation models to study the mass-action dynamics of DIPs and WT virus in the presence of adaptive and innate immunity that will otherwise clear the infection. Our goal is to understand whether the therapeutic administration of DIPs will augment or interfere with the immune response and, in the former case, we seek to provide guidance on how virus suppression is affected by infection and clearance parameters, as well as by the timing of DIP introduction. Consistent with previous theoretical work, we find that DIPs can significantly suppress viral load. When immunity is present, the timing of DIP administration matters, with an intermediate optimum. When successful at viral suppression, DIPs even slow the immune response, but the combined effect of DIPs and immunity is still beneficial. Outcomes depend somewhat on whether immunity is elicited by and clears DIPs, but timing appears to have the greater effect.