Pichinde virus belongs to the arenavirus family, which harbours several serious human pathogens. This work was performed in order to investigate the basis for the mouse-attenuated phenotype of a temperature sensitive mutant of Pichinde, and to identify potential genetic changes responsible. Since arenaviruses demonstrate a tropism for monocytes and macrophages, the ability of the mutant, ts13, to replicate in tissues enriched for these cells was assessed. Compared to the wild type (wt) parental virus, the mutant ts13 displayed markedly reduced replication in resident peritoneal cells (RPC) from infected mice, in both the macrophage-rich adherent population, and the non-adherent population, which is a mixture of monocytes and lymphocytes. This indicated that reduced growth in macrophages may be involved in the reduced growth of ts13 in vivo. This was further supported by the observation that the replication of ts13 was also limited in a macrophage cell line, and in RPC infected in vitro. Investigations such as those described here will provide valuable information regarding mechanisms of arenavirus attenuation, and the genetic changes required to limit growth and virulence. Ultimately, this will be of use in the design of effective arenaviral vaccines, which will become imperative in the midst of new and emerging arenaviral pathogens. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/4282 |
| Date | January 1998 |
| Creators | Gruber, Heidi. |
| Contributors | Wright, K., |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Detected Language | English |
| Type | Thesis |
| Format | 123 p. |
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