Author summary Hepatitis C virus affects approximately 70 million people worldwide, resulting in a significant impact on human health. The virus initiates infection through a complex set of interactions with proteins on the surface of human cells. Here we combine experimental approaches with a new mathematical model to study the process of viral entry. Our model is successful in capturing the behaviour of experiments, which show how changes in the amount of the human proteins CD81 and SR-B1 expressed by a cell alter the probability of a virus getting into a cell. Our model suggests that more than 10 CD81 receptors are needed to gain entry into a cell, and shows that viral entry is a difficult task, with many viruses failing at different stages of the entry process. Our model sets out a basis for further quantitative research into the process of HCV viral entry.
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