Up-regulation of a cellular protein at the translational level by a retrovirus.
Mink cell focus-forming (MCF) murine leukemia viruses (MLVs) are the etiologic agent of thymic lymphoma in mice. We have observed previously that superinfection by MCF13 MLV of certain cell types, such as preleukemic thymic lymphocytes and cultured mink epithelial cells, results in the accumulation of the viral envelope precursor polyprotein, leading to the induction of endoplasmic reticulum (ER) stress. In this study, we demonstrate that the induction of ER stress by MCF13 MLV infection results in an increase in the phosphorylation of the alpha-subunit of eukaryotic initiation factor 2. In cells in which this occurs, we have detected an up-regulation of the cellular inhibitor of apoptosis protein 1 (c-IAP1). The results of real-time RT-PCR quantification of message levels and protein turnover assays indicate that up-regulation of c-IAP1 occurs at the translational level. Elevation of c-IAP1 levels at a posttranscriptional step was detectable in MCF13 MLV-induced thymic lymphomas and chronically infected mink epithelial cells. The ability of a simple retrovirus to regulate cellular gene expression at the translational level may be an important mechanism that contributes to pathogenesis.
Yoshimura
Fayth K
FK
Department of Immunology and Microbiology and the Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA. fyoshi@med.wayne.edu
Luo
Xixia
X
Zhao
Xiaoqing
X
Gerard
Herve C
HC
Hudson
Alan P
AP
D000818:Animals; D004721:Endoplasmic Reticulum / Q000473:pathology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D009052:Leukemia Virus, Murine / Q000472:pathogenicity; D007942:Leukemia, Experimental / Q000209:etiology; D051379:Mice; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012190:Retroviridae / Q000472:pathogenicity*; D012192:Retroviridae Infections / Q000209:etiology; D013312:Stress, Physiological; D014412:Tumor Virus Infections / Q000209:etiology; D015854:Up-Regulation
D015852:Eukaryotic Initiation Factor-2; D051034:Inhibitor of Apoptosis Proteins