Regulation of PI3K/Akt dependent apoptotic markers during b virus infection of human and macaque fibroblasts
| Autor: | Julia K. Hilliard, Mugdha Vasireddi |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytomegalovirus Infection Viral Diseases viruses Herpesvirus 1 Cercopithecine lcsh:Medicine Apoptosis Pathogenesis Protein Synthesis Monkeys Pathology and Laboratory Medicine Macaque Biochemistry Phosphatidylinositol 3-Kinases Animal Cells Medicine and Health Sciences Phosphorylation lcsh:Science Connective Tissue Cells Mammals Multidisciplinary biology Cell Death Chemical Synthesis medicine.anatomical_structure Infectious Diseases Cell Processes Connective Tissue Medical Microbiology Viral Pathogens Vertebrates Host-Pathogen Interactions Viruses Cellular Types Anatomy Pathogens Research Article Primates Herpesviruses Biosynthetic Techniques Research and Analysis Methods Microbiology Virus 03 medical and health sciences biology.animal Virology Old World monkeys medicine Animals Humans Fibroblast Protein kinase B Microbial Pathogens PI3K/AKT/mTOR pathway 030102 biochemistry & molecular biology Biology and life sciences lcsh:R Intrinsic apoptosis Organisms Proteins Cell Biology Fibroblasts Viral Replication 030104 developmental biology Biological Tissue Viral replication Amniotes Macaca lcsh:Q DNA viruses Proto-Oncogene Proteins c-akt |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 5, p e0178314 (2017) |
| ISSN: | 1932-6203 |
| Popis: | B virus (Macacine herpesvirus 1), a simplex virus endemic in macaques, causes encephalitis, encephalomyelitis, and death in 80% of untreated zoonotically infected humans with delayed or no treatment. Here we report a significant difference in PI3K/Akt-dependent apoptosis between B virus infected human and macaque dermal fibroblasts. Our data show that B virus infection in either human or macaque fibroblasts results in activation of Akt via PI3K and this activation does not require viral de novo protein synthesis. Inhibition of PI3K with LY294002 results in a significant reduction of viral titers in B virus infected macaque and human fibroblasts with only a modest difference in the reduction of virus titers between the two cell types. We, therefore, tested the hypothesis that B virus results in the phosphorylation of Akt (S473), which prevents apoptosis, enhancing virus replication in B virus infected macaque dermal fibroblasts. We observed markers of intrinsic apoptosis when PI3K activation of Akt was inhibited in B virus infected macaque cells, while, these apoptotic markers were absent in B virus infected human fibroblasts under the same conditions. From these data we suggest that PI3K activates Akt in B virus infected macaque and human fibroblasts, but this enhances virus replication in macaque fibroblast cells by blocking apoptosis. |
| Databáze: | OpenAIRE |
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