Project name: Influenza A virus

Description: Defective interfering particles (DIPs) of influenza A virus (IAV) are naturally occurring mutants that comprise internal deletions in at least one of their eight viral RNA (vRNA) segments. Upon co-infection with infectious standard virus (STV), DIPs interfere with the viral replication cycle rendering them candidates for antiviral therapy. To study the propagation competition between defective interfering (DI) vRNAs, we used a small-scale two-stage cultivation system for semi-continuous propagation of IAV. Strong periodic oscillations in virus titers were observed due to the dynamic interaction of DIPs and STV. Using next generation sequencing, we found a predominant formation and accumulation of DI vRNAs on the polymerase segments. Short DI vRNAs accumulated stronger than longer ones, indicating a replication advantage. However, a sweet spot of fragment length was observed. Some DI vRNAs, including highly accumulated ones, showed breaking points in a specific part of their bundling signal, suggesting its dispensability for DI vRNA propagation. Over a total cultivation time of 21 days post infection, several distinct DI vRNAs accumulated to high levels, while others decreased. Assuming that DIPs replicating to high copy numbers have a high capacity to interfere with STV replication, we suggest candidates for efficacious antiviral treatment.

Data type: raw sequence reads

Sample scope: Monoisolate

Relevance: Medical

Last updated: 2021-07-02