期刊
JOURNAL OF VIROLOGY
卷 82, 期 16, 页码 8000-8012出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.02752-07
关键词
-
类别
资金
- NCI NIH HHS [R01 CA124309] Funding Source: Medline
Promyelocytic Leukemia nuclear body (PML NB) proteins mediate an intrinsic cellular host defense response against virus infections. Herpesviruses express proteins that modulate PML or I'ML-associated proteins by a variety of strategies, including degradation of PML or relocalization of PML NB proteins. The consequences of PML-herpesvirus interactions during infection in vivo have yet to be investigated in detail, largely because of the species-specific tropism of many human herpesviruses. Murine gammaherpesvirus 68 (gamma HV68) is emerging as a suitable model to study basic biological questions of virus-host interactions because it naturally infects mice. Therefore, we sought to determine whether gamma HV68 targets PML NBs as part of its natural life cycle. We found that gamma HV68 induces PML degradation through a proteasome-dependent mechanism and that loss of PML results in more robust virus replication in mouse fibroblasts. Surprisingly, THV68-mediated PML degradation was mediated by the vition tegument protein ORF75c, which shares homology with the cellular formylglycinamide ribotide amidotransferase enzyme. In addition, we show that ORF75c is essential for production of infectious virus. ORF75 homologs are conserved in all rhadinoviruses but so far have no assigned functions. Our studies shed light on a potential role for this unusual protein in rhadinovirus biology and suggest that THV68 will be a useful model for investigation of PMIherpesvirus interactions in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据