1. The lack of RNA-dependent protein kinase enhances susceptibility of mice to genital herpes simplex virus type 2 infection
- Author
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Robert H. Silverman, Daniel J.J. Carr, Lisa Tomanek, Todd Wuest, and Bryan R.G. Williams
- Subjects
CD3 Complex ,viruses ,Herpesvirus 2, Human ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Biology ,CD8-Positive T-Lymphocytes ,Virus ,Interferon-gamma ,Mice ,eIF-2 Kinase ,medicine ,2',5'-Oligoadenylate Synthetase ,Immunology and Allergy ,Cytotoxic T cell ,Animals ,Lymphocyte Count ,Protein kinase A ,Chemokine CCL4 ,Lymph node ,Chemokine CCL3 ,Mice, Knockout ,EIF-2 kinase ,Herpes Genitalis ,Tumor Necrosis Factor-alpha ,Original Articles ,Macrophage Inflammatory Proteins ,Flow Cytometry ,Protein kinase R ,Virology ,Mice, Inbred C57BL ,Titer ,medicine.anatomical_structure ,Spinal Cord ,Chemokines, CC ,biology.protein ,Female ,Disease Susceptibility ,Lymph Nodes ,CD8 ,Brain Stem - Abstract
Mice deficient in RNA-dependent protein kinase (PKR -/- ) or deficient in PKR and a functional 2',5'-oligoadenylate synthetase (OAS) pathway (PKR/RL -/- ) are more susceptible to genital herpes simplex virus type 2 (HSV-2) infection than wild-type mice or mice that are deficient only in a functional OAS pathway (RL -/- ) as measured by survival over 30 days. The increase in susceptibility correlated with an increase in virus titre recovered from vaginal tissue or brainstem of infected mice during acute infection. There was also an increase in CD45 + cells and CD8 + T cells residing in the central nervous system of HSV-2-infected PKR/RL -/- mice in comparison with RL -/- or wild-type control animals. In contrast, there was a reduction in the HSV-specific CD8 + T cells within the draining lymph node of the PKR/RL -/- mice. Collectively, activation of PKR, but not of OAS, contributes significantly to the local control and spread of HSV-2 following genital infection.
- Published
- 2006