Host factors influencing viral persistence

With the aim of characterizing the antiviral immune response to a non-cytoc idal virus, we studied the outcome of lymphocytic choriomeningitis virus in fection in a number of gene knockout mouse strains. Two virus strains diffe ring markedly in their capacity to spread and replicate inside the murine h ost were used. Our results reveal that very different outcomes may be obser ved depending on Virus strain and immunocompetence of the host. Thus while CD4(+) cells are not critical during the initial phase of virus control, in fectious virus reappear in mice lacking CD4(+) cells, B cells or CD40 ligan d. Reappearance of virus is associated with impaired long-term CD8(+) T-cel l mediated immune surveillance, and the time to virus resurgence is inverse ly correlated to the replication rate of the virus. Our studies also reveal that interferon-gamma is a central cytokine, and depending on the rate of virus replication, mice lacking the ability to product: interferon-gamma ma y develop either a severe, mostly fatal, T-cell mediated wasting syndrome o r a chronic infection characterized by long-term coexistence of antiviral c ytotoxic T lymphocytes and infectious virus. Mathematical modelling indicat es that these different outcomes may be explained in relatively simple math ematical terms. This suggests that modelling may be used as a means to pred ict critical host and virus parameters. Therefore, combining mathematical m odelling with precise, quantitative, in vine analyses looks to be a promisi ng approach in addressing central quantitative issues in immunobiology.