Cuchet-Lourenço, D., Anderson, G., Sloan, E. , Orr, A. and Everett, R.D. (2013) The viral ubiquitin ligase icp0 is neither sufficient nor necessary for degradation of the cellular dna sensor ifi16 during herpes simplex virus 1 infection. Journal of Virology, 87(24), pp. 13422-13432. (doi: 10.1128/JVI.02474-13) (PMID:24089555) (PMCID:PMC3838218)
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Abstract
The cellular protein IFI16 colocalizes with the herpes simplex virus 1 (HSV-1) ubiquitin ligase ICP0 at early times of infection and is degraded as infection progresses. Here, we report that the factors governing the degradation of IFI16 and its colocalization with ICP0 are distinct from those of promyelocytic leukemia protein (PML), a well-characterized ICP0 substrate. Unlike PML, IFI16 colocalization with ICP0 was dependent on the ICP0 RING finger and did not occur when proteasome activity was inhibited. Expression of ICP0 in the absence of infection did not destabilize IFI16, the degradation occurred efficiently in the absence of ICP0 if infection was progressing efficiently, and IFI16 was relatively stable in wild-type (wt) HSV-1-infected U2OS cells. Therefore, IFI16 stability appears to be regulated by cellular factors in response to active HSV-1 infection rather than directly by ICP0. Because IFI16 is a DNA sensor that becomes associated with viral genomes during the early stages of infection, we investigated its role in the recruitment of PML nuclear body (PML NB) components to viral genomes. Recruitment of PML and hDaxx was less efficient in a proportion of IFI16-depleted cells, and this correlated with improved replication efficiency of ICP0-null mutant HSV-1. Because the absence of interferon regulatory factor 3 (IRF3) does not increase the plaque formation efficiency of ICP0-null mutant HSV-1, we speculate that IFI16 contributes to cell-mediated restriction of HSV-1 in a manner that is separable from its roles in IRF3-mediated interferon induction, but that may be linked to the PML NB response to viral infection.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Everett, Professor Roger and Orr, Mrs Anne and Cuchet, Dr Delphine and Sloan, Dr Elizabeth |
| Authors: | Cuchet-Lourenço, D., Anderson, G., Sloan, E., Orr, A., and Everett, R.D. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Journal of Virology |
| Publisher: | American Society for Microbiology |
| ISSN: | 0022-538X |
| ISSN (Online): | 1098-5514 |
| Published Online: | 19 November 2013 |
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