Mammalian reovirus (MRV) is a prototype virus of Reoviridae family. MRV virions are composed of two concentric protein capsids that surround a genome of 10 segments of dsRNA. It has been shown that MRV can manipulate host gene expression and further induce apoptosis and cell cycle arrest in various cell lines. However, the detailed molecular mechanisms by which MRV regulates the expression of host cells are largely unknown. P53 is an important transcriptional factor which modulates the expression of more than 130 genes controlled in cell stress-response. We aimed to examine the molecular mechanisms underlying the effect of MRV infection on the expression of host genes and the possible role of p53 in the interaction of MRV and host cells. Prototype serotype 3 reovirus strain Dearing (T3D) and serotype 1 strain Lang (T1L) were used to infect different cell lines, respectively, H1299 (p53-null and p53 positive), HT1080 (p53 mutant and p53 positive) and HCT116 (p21 deficient and 14-3-3σ deficient).
By comparing the virus replication curve of T1L and T3D in these cell lines, we found that MRV can replicate with a similar pattern in both p53-defective and p53-positive cell lines which indicated that p53 does not have significant impact on MRV replication in these cell lines.
We further found that the level of Bcl-xL protein, which has been shown to be able to inhibit apoptosis, was increased in H1299 cell lines (both p53-null and p53 positive) infected by T3D, but decreased in the same cell lines infected by T1L. A similar change of Bcl-xL protein was not observed In HCT116 and HT1080 cell lines with MRV infection. Fifty four T1L×T3D reassortants were used to map which gene or gene combination was responsible for the changes of Bcl-xL protein. We found that the expression of Bcl-xL protein in H1299 cell line infected by MRV was majorly controlled by the S1 gene segment which encodes the σ1 cell attachment protein and the σ1s non structural protein, while minorly controlled by L3 gene segment of MRV.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:MWU.1993/4221 |
| Date | 22 September 2010 |
| Creators | Wang, Lou |
| Contributors | Coombs, Kevin M. (Medical Microbiology), Mowat, Michael R. (Biochemistry and Medical Genetics) Alfa, Michelle J. (Medical Microbiology) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_US |
| Detected Language | English |
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