Publication date: Available online 29 March 2018
Source:Cell Host & Microbe
Author(s): Jagadish Beloor, Nyree Maes, Irfan Ullah, Pradeep Uchil, Andrew Jackson, Erol Fikrig, Sang Kyung Lee, Priti Kumar
No vaccines or therapeutics are licensed for West Nile virus (WNV), a mosquito-transmitted neuroencephalitic flavivirus. The small interfering RNA siFvEJW targets a conserved sequence within the WNV E protein and limits virus infection. Using a rabies virus-derived neuron-targeting peptide (RVG9R) and an intranasal route for delivering siFvEJW to the CNS, we demonstrate that treatment of WNV-infected mice at late stages of neuroinvasive disease results in recovery. Selectively targeting virus in the CNS lowers viral burdens in the brain, reduces neuropathology, and results in a 90% survival rate at 5–6 days post-infection (when viral titers peak in the CNS), while placebo-treated mice succumb by days 9–10. Importantly, CNS virus clearance is achieved by humoral and cell-mediated immune responses to WNV infection in peripheral tissues, which also engender sterilizing immunity against subsequent WNV infection. These results indicate that intranasal RVG9R-siRNA treatment offers efficient late-stage therapy and facilitates natural long-term immunity against neuroinvasive flaviviruses.
Graphical abstract
Teaser
No vaccines or therapies exist for WNV disease. Beloor et al. show that intranasal treatment with a neuron-penetrating peptide complexed to antiflaviviral siRNAs is therapeutic for neuroinvasive WNV disease. The approach reduces CNS viral burden, allowing development of immune responses to WNV. This enables recovery and protects against future WNV infection.https://ift.tt/2J7K5eD
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