Evolving cell death in the virus-infected nervous system.

611 In a recent article 1 , Allsopp and Fazakerley presented evidence supporting the view that the death of nerve cells upon infection with virus might be viewed as an adaptation by the host to minimize the spread of infection throughout the nervous system. Such 'altruistic' cell suicide will presumably have evolved through kin selection 2 among clonal cell lineages, whereby infected cells not contributing directly to the germ line undergo apopto-sis, and thereby reduce the impact of infection on the fitness of the organism as a whole. This assumes that the loss of a few infected cells outweighs the potential cost of a more sweeping infection. Allsopp and Fazakerley highlight the intriguing state-dependent sensitivity of cells to undergo cell death, where immature neur-ones are more susceptible to apoptosis than mature neurones. Given such an evolutionary conflict of interest between a parasite and its host, it is often useful to characterize in formal terms the parametric dependencies of the interaction. In an earlier paper 3 , Robert Payne and I sought to derive mathematical conditions for the induction of apoptosis by either a virus or the infected cell. It is often uncertain which party initiates cell death, and hence one cannot always assume that apoptosis is in the host's best interest. Apoptosis could be undesirable for both the virus and the host, or even benefit the virus to the detriment of the host. The mathematical model seeks to classify the outcomes of the infection into host-induced, versus virus-induced cell death, and relates these outcomes to the productivity of infection, the average life span of the cell and the leakage of virions during apoptosis. The mathematical model considers uninfected cells, free virus and infected cells. Upon infection, the host cells and the virus both have access to pathways culminating in expression of pro-apoptotic genes. Infected cells have a natural (non-apoptotic) death rate described by the rate parameter µ. Virions are released from infected cells at a rate α. Upon programmed death of the cell, a quantity ␬ virions are released. With these three parameters one can derive the expression: ∆ = α/µ – ␬ The right-hand side of this equation can be interpreted as the average number of virions produced by the infected cell without the induction of cell death (or lysis) minus the average number of virions produced upon cell death alone. The sign and magnitude of ∆ provides a …