Investigating viremia rebounds using a PRSS data-supported model of immune response
Abstract
Viremia rebound is a common but undesirable phenomenon
for various diseases, especially for the Porcine
Respiratory and Reproductive Syndrome (PRRS), a major
concern for the swine industry. What causes some
individuals to experience viremia rebound while others
manage to steadily clear the virus has however been
subject to much speculation. Hypotheses are the
emergence of viral escape mutants, re-infection and
differences in immune competence.
To test this
last hypothesis, we developed a mathematical model
describing the within-host immune response to PRRS
infection. We included the major mechanisms found to
influence PRRS infection, as well as their regulations
at the between-cell scale. We developed a rigorous
ABC-like optimisation method to fit our model to an
extensive set of experimental data, consisting of
non-rebounder and rebounder viremia profiles. We then
compared, between both profiles, the estimated
parameter values, the resulting immune dynamics and
the efficacy of the underlying immune mechanisms.
Confronted to experimental data, our model
successfully captured the between-host variations
observed in viremia data, including rebounds.
Moreover, we found that rebound was promoted by high
apoptosis, high cell infection and low cytolysis by
cytotoxic lymphocytes, while increasing neutralisation
was very efficient to prevent rebounds. These results
show that viremia rebound can occur as a result of
differences in the immune competence alone and offers,
for the first time, insights into potential causative
immune mechanisms generating rebound.