| First Author | Prestwood TR | Year | 2012 |
| Journal | J Virol | Volume | 86 |
| Issue | 23 | Pages | 12561-70 |
| PubMed ID | 22973027 | Mgi Jnum | J:189016 |
| Mgi Id | MGI:5444066 | Doi | 10.1128/JVI.06743-11 |
| Citation | Prestwood TR, et al. (2012) Gamma Interferon (IFN-gamma) Receptor Restricts Systemic Dengue Virus Replication and Prevents Paralysis in IFN-alpha/beta Receptor-Deficient Mice. J Virol 86(23):12561-70 |
| abstractText | We previously reported that mice lacking alpha/beta and gamma interferon receptors (IFN-alpha/betaR and -gammaR) uniformly exhibit paralysis following infection with the dengue virus (DENV) clinical isolate PL046, while only a subset of mice lacking the IFN-gammaR alone and virtually no mice lacking the IFN-alpha/betaR alone develop paralysis. Here, using a mouse-passaged variant of PL046, strain S221, we show that in the absence of the IFN-alpha/betaR, signaling through the IFN-gammaR confers approximately 140-fold greater resistance against systemic vascular leakage-associated dengue disease and virtually complete protection from dengue-induced paralysis. Viral replication in the spleen was assessed by immunohistochemistry and flow cytometry, which revealed a reduction in the number of infected cells due to IFN-gammaR signaling by 2 days after infection, coincident with elevated levels of IFN-gamma in the spleen and serum. By 4 days after infection, IFN-gammaR signaling was found to restrict DENV replication systemically. Clearance of DENV, on the other hand, occurred in the absence of IFN-gammaR, except in the central nervous system (CNS) (brain and spinal cord), where clearance relied on IFN-gamma from CD8(+) T cells. These results demonstrate the roles of IFN-gammaR signaling in protection from initial systemic and subsequent CNS disease following DENV infection and demonstrate the importance of CD8(+) T cells in preventing DENV-induced CNS disease. |
