Low level viral persistence after infection with LCMV: a quantitative insight through numerical bifurcation analysis

Many important viruses persist at very low levels in the body in the face o f host immunity, and may influence the maintenance of this state of 'infect ion immunity'. To analyse low level viral persistence in quantitative terms , we use a mathematical model of antiviral cytotoxic T lymphocyte (CTL) res ponse to lymphocytic choriomeningitis virus (LCMV). This model, described b y a non-linear system of delay differential equations (DDEs), is studied us ing numerical bifurcation analysis techniques for DDEs. Domains where low l evel LCMV coexistence with CTL memory is possible, either as an equilibrium state or an oscillatory pattern, are identified in spaces of the model par ameters characterising the interaction between virus and CTL populations. O ur analysis suggests that the coexistence of replication competent virus be low the conventional detection limit (of about 100 pfu per spleen) in the i mmune host as an equilibrium state requires the per day relative growth rat e of the virus population to decrease at least 5-fold compared to the acute phase of infection. Oscillatory patterns in the dynamics of persisting LCM V and CTL memory, with virus population varying between 1 and 100 pfu per s pleen, are possible within quite narrow intervals of the rates of virus gro wth and precursor CTL population death. Whereas the virus replication rate appears to determine the stability of the low level virus persistence, it d oes not affect the steady-state level of the viral population, except for v ery low values. (C) 2001 Published by Elsevier Science Inc.