Viral Aggregation: The Knowns and Unknowns

Viral aggregation is a complex and pervasive phenomenon affecting many viral families. An increasing number of studies have indicated that it can modulate critical parameters surrounding viral infections, and yet its role in viral infectivity, pathogenesis, and evolution is just beginning to be appreciated. Aggregation likely promotes viral infection by increasing the cellular multiplicity of infection (MOI), which can help overcome stochastic failures of viral infection and genetic defects and subsequently modulate their fitness, virulence, and host responses. Conversely, aggregation can limit the dispersal of viral particles and hinder the early stages of establishing a successful infection. The cost-benefit of viral aggregation seems to vary not only depending on the viral species and aggregating factors but also on the spatiotemporal context of the viral life cycle. Here, we review the knowns of viral aggregation by focusing on studies with direct observations of viral aggregation and mechanistic studies of the aggregation process. Next, we chart the unknowns and discuss the biological implications of viral aggregation in their infection cycle. We conclude with a perspective on harnessing the therapeutic potential of this phenomenon and highlight several challenging questions that warrant further research for this field to advance.