Meher Sethi, Emory University

Meher Sethi1, David VanInsberghe1, Anice C. Lowen1,2 1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA 2Emory Center of Excellence for Influenza Research and Response (CEIRR), Atlanta, GA, USA

Cell Biology of Viral Infection

Viral spread is classically thought to be mediated predominately by single viral particles. However, there is growing evidence that collective dispersal plays an important role in diverse viral systems. Many viruses travel inside membranous vesicles, cluster onto bacterial surfaces, bind to cellular or fecal substrate, and/or aggregate in the extracellular milieu. The resultant groups of viruses then mediate dissemination. However, the role of collective dispersal in shaping viral evolutionary outcomes remains ambiguous. We hypothesized that collective dissemination would modulate viral infection dynamics and increase the opportunity for genetic exchange. To test this hypothesis, we established a system for inducing aggregation in mammalian orthoreovirus, a segmented double strand RNA virus, by manipulating pH and ionic concentration. Using transmission electron microscopy (TEM), we show that aggregation promotes coordinated delivery of viruses to cells and increases the number of viruses entering per cell. Consistent with this observation, we found that both the number of foci of infection and the amount of progeny virus produced through infection were reduced by aggregation. However, by examining co-infection between viruses with silent genetic markers, we found that the prevalence of mixed infection and levels of genetic exchange via reassortment were significantly increased with aggregation. Thus, collective dissemination of mammalian orthoreovirus lowers its replicative potential but increases its evolutionary potential by promoting genetic diversification.