(692f) Genome-Level Quantification of the Population Dynamics of Virus and Virus-Like Defective Interfering Particles

Viruses carry genes that can reprogram an infected cell to produce hundreds or thousands of progeny virus particles. Populations of progeny particles include both infectious and non-infectious particles. One class of non-infectious particles carry genomes that contain one or more deletions in essential viral functions, but they retain promoter sequences that are recognized by the viral polymerase. The genomes of such defective particles are able to replicate when defective and infectious virus particles co-infect the same cell.  The resulting competition between defective and intact virus genomes for viral and cellular resources interferes with the normal production of infectious virus progeny.  Defective interfering (DI) particles have been identified for virtually all viruses.  However, open questions remain on how DI particles emerge from virus-cell interactions, how their genomic structure impacts their ability to interfere with virus infections, the role of DI particles in the pathogenesis of viral diseases such as AIDS, influenza, and hepatitis C, and the extent to which DI particles may be engineered for biomedical applications.  To begin to address these questions we study a model RNA virus, vesicular stomatitis virus (VSV) and its production of virus and DI particles when infecting baby hamster kidney (BHK21) cells.  Here, we employed Illumina sequencing and quantitative RT-PCR to characterize the population dynamics of DI particles relative to infectious virus particles across multiple co-infection cycles.  By combining our genomic analysis with independent measures of biological activity of DI and infectious particles we propose a quantitative and mechanistic perspective of co-infection and interference.  These results suggest ways DI particles may impact the dynamics of natural infections and open avenues for new anti-viral strategies based on the engineering of DI particles.