The way in which a viral infection spreads within a host is a complex process that is not well understood. Different viruses, such as human immunodeficiency virus type 1 and hepatitis C virus, have evolved different strategies, including direct cell-to-cell transmission and cell-free transmission, to spread within a host. To what extent these two modes of transmission are exploited in vivo is still unknown. Mathematical modeling has been an essential tool to get a better systematic and quantitative understanding of viral processes that are difficult to discern through strictly experimental approaches. In this review, we discuss recent attempts that combine experimental data and mathematical modeling in order to determine and quantify viral transmission modes. We also discuss the current challenges for a systems-level understanding of viral spread, and we highlight the promises and challenges that novel experimental techniques and data will bring to the field.
Keywords: HCV; HIV; agent-based models; cell-free virus infection; cell-to-cell infection; mathematical modeling.