EEE Seminar: control engineering to analyse measles.

Control analysis of the measles paradox reveals how the balance between the production and killing of infected lymphocytes determines viral clearance

ABSTRACT

The measles paradox refers to the apparent contradiction of severe immunosuppression by measles virus (MV) followed by viral clearance [1, 2]. Previous experimental and mathematical studies in [1–4] suggested that viral clearance is regulated differently for measles and canine distemper virus (CDV) during acute infection. It is sensible to advance the understanding of the control of viral clearance in vivo because measles and CDV are a major cause of death for animals and humans [4, 5]. We study what determines the control of acute viremia in the virus-host interactions for measles and CDV.

We build on recent mathematical models from [2] which describe the within-host dynamics of measles and CDV during acute infection; we investigate control mechanisms to achieve viral clearance by applying control theory [6–9]. The results highlight an analytical condition to predict and monitor the clearance of acute viremia. Viral clearance occurs despite virus-induced immunosuppression when the within-host dynamics satisfy this condition. When the killing action of measles-specific T cells becomes sufficient to satisfy the proposed condition, the killing action exceeds the production of infected lymphocytes and the MV-specific T cell response enforces the clearance of acute measles infection. In contrast, the killing action of CDV-specific T cells is impaired because the extensive predation of CDV leads to an extreme depletion of CDV-specific T cells. The depletion of lymphocytes enforces the clearance of acute CDV infection. Modelling uncertainties discussed in [2] may have a bearing on these results.

Together, the findings suggest that the balance between the production and killing of infected lymphocytes determines the control of acute viremia for both measles and CDV. Moreover, this novel framework delivers mechanistic insights to determine the success or failure of viral clearance, and thus predict requirements for effective treatments.

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