CD8+ T cells use TRAIL to restrict west nile virus pathogenesis by controlling infection in neurons

Bimmi Shrestha, Amelia K. Pinto, Sharone Green, Irene Bosch, Michael S. Diamond

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Previous studies of mice have demonstrated that an orchestrated sequence of innate and adaptive immune responses is required to control West Nile virus (WNV) infection in peripheral and central nervous system (CNS) tissues. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL; also known as CD253) has been reported to inhibit infection with dengue virus, a closely related flavivirus, in cell culture. To determine the physiological function of TRAIL in the context of flavivirus infection, we compared the pathogenesis of WNV in wild-type and TRAIL-/- mice. Mice lacking TRAIL showed increased vulnerability and death after subcutaneous WNV infection. Although no difference in viral burden was detected in peripheral tissues, greater viral infection was detected in the brain and spinal cord at late times after infection, and this was associated with delayed viral clearance in the few surviving TRAIL-/- mice. While priming of adaptive B and T cell responses and trafficking of immune and antigen-specific cells to the brain were undistinguishable from those in normal mice, in TRAIL-/- mice, CD8+ T cells showed qualitative defects in the ability to clear WNV infection. Adoptive transfer of WNV-primed wild-type but not TRAIL-/- CD8+ T cells to recipient CD8-/- mice efficiently limited infection in the brain and spinal cord, and analogous results were obtained when wild-type or TRAIL-/- CD8+ T cells were added to WNV-infected primary cortical neuron cultures ex vivo. Collectively, our results suggest that TRAIL produced by CD8+ T cells contributes to disease resolution by helping to clear WNV infection from neurons in the central nervous system.

Original languageEnglish
Pages (from-to)8937-8948
Number of pages12
JournalJournal of virology
Volume86
Issue number17
DOIs
StatePublished - Sep 1 2012

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