The lack of RNA-dependent protein kinase enhances susceptibility of mice to genital herpes simplex virus type 2 infection.
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.
Carr
Daniel J J
DJ
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. dan-carr@ouhsc.edu
Wuest
Todd
T
Tomanek
Lisa
L
Silverman
Robert H
RH
Williams
Bryan R G
BR
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000818:Animals; D001933:Brain Stem / Q000821:virology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000032:analysis; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006558:Herpes Genitalis / Q000201:enzymology* / Q000276:immunology; D018258:Herpesvirus 2, Human; D007371:Interferon-gamma / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology; D018655:Lymphocyte Count; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013116:Spinal Cord / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019892:eIF-2 Kinase / Q000235:genetics*
D017252:CD3 Complex; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019892:eIF-2 Kinase; D015088:2',5'-Oligoadenylate Synthetase