Friend virus (FV) causes erythroleukemia and immunosuppression in susceptible mouse strains. Many studies have examined FV induced suppression of both humoral and cellular immunity. However, few studies have focused on differences in disease development in young and aged mice. This study will establish the differences in susceptibility between young and aged mice and determine the mechanism for this age related difference. Specifically I will: 1. Confirm our observation that FV induced disease is decreased in aged versus young mice. This will be accomplished by determining the degree of splenomegaly. 2. Examine difference in viral replication and expression of FV in target organsof young and aged mice. Replication of herpes virus will be determined by x c assay, of spleen focus forming virus by enumerating spleen foci, and total virus expression by reverse transcriptase activity. Virus expression will be further explored using Western and Northern blot analysis to examine specific viral products. 3. Determine if there are age related differences in the number of target cells, range of target cells, or the ability of target cells to sustain a viral infection using flow cytometry to detect changes in cell type and number and in situ hybridization to detect viral replication. Further, host gene loci have been demonstrated to alter FV replication and disease changes in erythroprotein receptor and C-kit will be examined by antibody techniques, Northern analysis and, if necessary, DNA sequencing maturation, changes in these loci can lead to changes in cell development. Therefore, loci that effect FV susceptibility or receptors that are regulated by the loci will be examined. Friend virus in an aging mouse model is an excellent system to gain information on how other retroviruses with similar life cycles replicate in young verses aged animals .and will give new insights regarding approaches to human HIV studies.
| Stewart, D R; Kirschmann, D A; Blank, K J et al. (1994) Differences between young and aged mice in susceptibility to Friend virus. Mech Ageing Dev 73:145-55 |
