Infection of IFNγ receptor knockout (IFNγ R-/-) mice with murine gammaherpesvirus-68 (MHV-68) results in fibrosis in the lung, spleen, liver and lymph nodes. In the spleen, pathology involves an increase in the number of latently infected B cells that corresponds with a Th2 biased immune response, in which germinal centres become walled off and fibrosis dominates the splenic architecture. Remarkably, the spleen recovers from this pathology, and the starting point for this process is a loss of latently infected B cells. The aim of this project is to gain further understanding of the control of MHV-68 latent infection in the absence of IFNγ response. This project investigates: (1) the mechanisms that result in the loss of splenocytes, in particular the reduction of latently infected B cells; (2) the dynamics of macrophages in the induction, expression and recovery of fibrosis. Several approaches were employed to examine the hypothesis that the massive cell loss in IFNγR-/- spleen is caused by apoptosis. However, there was no evidence for excessive apoptosis throughout the development of fibrosis. Moreover, RT-PCR analysis showed that there was no significant increase in expression of viral genes associated with lytic infection. Hence it is unlikely that viral reactivation and subsequent lytic infection occurs. These data suggest apoptosis and viral reactivation are not the main mechanisms that cause splenic cell loss. Furthermore, B cell subpopulations and cells that express viral ORF73 in IFNγR-/- mice were examined using a recombinant virus. The ORF73-expressing cells are mainly germinal centre B cells and memory B cells. These two subpopulations undergo a drastic decrease in numbers during fibrosis, whereas naïve B cells, which are less susceptible to infection, maintain a relatively stable population. Therefore, the significant reduction of latently infected B cells appears to be related to the removal of germinal center B cells and memory B cells. Macrophages induced by Th2 cytokines are considered to be pro-fibrotic, and they are reported to have the potential to differentiate into myofibroblasts. In order to determine the role played by macrophages in MHV-68 induced fibrosis, transgenic mice with eGFP constitutively expressed in macrophages and dendritic cells were used. A different pattern of macrophage distribution in IFNγR-/- mice was observed compared to that in wild type mice. Moreover, the number of splenic macrophages changed dramatically in the spleen at different stages of fibrosis. The possibility that alternatively activated macrophages differentiate into myofibroblasts was investigated by co-staining with α-SMA antibody. However, no evidence was found that macrophages are one of the origins of myofibroblasts. This suggests macrophages may play other roles in regulating fibrosis rather than contributing directly to the formation of fibrosis.