Modelling The Evolutionary Dynamics of Hepatitis C Virus

Dr Fabio Luciani, School of Medical sciences, University of New South Wales, Australia
Tuesday June 9 , Location: Room 707 Department of Mathematics UCL, Time: 16.30

In this model we study the evolutionary dynamics of a rapidly mutating virus and investigate mechanisms leading to chronic infections. We develop a nested-model approach that incorporates within-host evolutionary dynamics of a rapidly mutating virus (hepatitis C virus, HCV) targeted by a cellular cross-reactive immune response, into an epidemiological perspective. The viral trait we follow at the between-host level is the replication rate of the strain initiating the infection.
We find that, even for rapidly evolving viruses, the replication rate of the initial strain has a strong effect on the fitness of an infection and that it can be heritable from one infection to the next. Moreover, we find that infections caused by slowly replicating viruses have the highest fitness (i.e., lead to more secondary infections). We also study the effect of cross-reactive immunity and viral mutation rate on infection life history traits. Because of the stochastic nature of our approach, we can identify the factors affecting the outcome of the infection (acute or chronic infections). Finally, we show that anti-viral treatments affect the value of the optimal initial replication rate and that starting the treatment too early in the infection can have deleterious consequences because of within-host evolution.
Our results support the idea that natural selection can act on the replication rate of rapidly evolving viruses at the between-host level. It also provides a mechanistic description of within-host constraints, such as cross-reactive immunity, and shows how such constraints affect the infection fitness. Finally, we will discuss the model validation within the context of the Hepatitis C Incidence and Transmission Study (HITS), an ongoing study that aims at evaluating the incidence and prevalence of HCV in prisons of New South Wales, Australia.

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