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| Status |
Public on Apr 03, 2008 |
| Title |
Herpes simplex host shutoff attenuates antiviral state |
| Platform organism |
Human alphaherpesvirus 1 |
| Sample organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Herpes simplex virus mutants lacking the vhs gene are severely attenuated in animal models of pathogenesis and exhibit reduced growth in primary cell culture. As a result of these properties vhs-deleted virus have been proposed as live-attenuated viruses. Despite these findings and their implications for vacccines, the mechanisms by which vhs promotes infection in cell culture and in vivo are not understood. In this study we demonstrate that vhs-deficent viruses replicate to reduced levels in interferon(IFN)- primed cells. Furthermore, vhs-defective viruses induce increased levels of IFNβ and IFNβ-stimulated genes, and increased levels of eIF2α phosphorylation in infected cells. In addition, we demonstrate a generalized over-expression of viral RNAs following infection with a vhs-deficient virus. This suggests increased expression of IFN pathway inducing double stranded RNA, a potent pathogen-associated molecular pattern (PAMP). Together these data show that vhs likely functions to reduce innate immune responses and thereby acts as critical determinant of viral pathogenesis.
Keywords: time course, genetic modification
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| Overall design |
Time course (1,3,6,9 & 12h) of HSV infected mouse embryo fibroblasts. Wild type (KOS) virus is co-hybridized with vhs null virus (NHB). Each time-point is hybridized in quadruplicate.
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| |
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| Contributor(s) |
Crosby SD, Pasieka T, Alexander DE, Leib DA |
| Citation(s) |
18367525 |
| |
| Submission date |
Mar 27, 2008 |
| Last update date |
Mar 19, 2012 |
| Contact name |
Seth Daniel Crosby |
| E-mail(s) |
scrosby@wustl.edu
|
| Phone |
314-286-1256
|
| Organization name |
Washington Univeristy School of Medicine
|
| Department |
Genetics
|
| Lab |
GTAC
|
| Street address |
660 S. Euclid
|
| City |
St. Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
| |
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| Platforms (1) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA107163 |
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