| Title: |
Myxoma Virus M-T5 Protects Infected Cells from the Stress of Cell Cycle Arrest through Its Interaction with Host Cell Cullin-1 |
| Authors: |
Johnston, J. B.; Wang, G.; Barrett, J. W.; Nazarian, S. H.; Colwill, K.; Moran, M.; McFadden, G. |
| Source: |
Journal of Virology ; volume 79, issue 16, page 10750-10763 ; ISSN 0022-538X 1098-5514 |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2005 |
| Description: |
The myxoma virus (MV) M-T5 gene encodes an ankyrin repeat protein that is important for virus replication in cells from several species. Insight was gained into the molecular mechanisms underlying the role of M-T5 as a host range determinant when the cell cycle regulatory protein cullin-1 (cul-1) was identified as a cellular binding partner of M-T5 and found to colocalize with the protein in both nuclear and cytosolic compartments. Consistent with this interaction, infection with wild-type MV (vMyxlac) or a deletion mutant lacking M-T5 (vMyxT5KO) differentially altered cell cycle progression in a panel of permissive and nonpermissive cells. Cells infected with vMyxlac transitioned rapidly out of the G 0 /G 1 phase and preferentially accumulated at the G 2 /M checkpoint, whereas infection with vMyxT5KO impeded progression through the cell cycle, resulting in a greater percentage of cells retained at G 0 /G 1 . Levels of the cul-1 substrate, p27/Kip-1, were selectively increased in cells infected with vMyxT5KO compared to vMyxlac, concurrent with decreased phosphorylation of p27/Kip-1 at Thr187 and decreased ubiquitination. Compared to cells infected with vMyxlac, cell death was increased in vMyxT5KO-infected cells following treatment with diverse stimuli known to induce cell cycle arrest, including infection itself, serum deprivation, and exposure to proteasome inhibitors or double-stranded RNA. Moreover, infection with vMyxlac, but not vMyxT5KO, was sufficient to overcome the G 0 /G 1 arrest induced by these stimuli. These findings suggest that M-T5 regulates cell cycle progression at the G 0 /G 1 checkpoint, thereby protecting infected cells from diverse innate host antiviral responses normally triggered by G 0 /G 1 cell cycle arrest. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1128/jvi.79.16.10750-10763.2005 |
| DOI: |
10.1128/JVI.79.16.10750-10763.2005 |
| Availability: |
https://doi.org/10.1128/jvi.79.16.10750-10763.2005; https://journals.asm.org/doi/pdf/10.1128/JVI.79.16.10750-10763.2005 |
| Rights: |
https://journals.asm.org/non-commercial-tdm-license |
| Accession Number: |
edsbas.F310E79A |
| Database: |
BASE |