Abstract
West Nile virus (WNV) typically leads to asymptomatic infection but can cause severe neuroinvasive disease or death, particularly in the elderly. Innate NK cells play a critical role in antiviral defenses, yet their role in human WNV infection is poorly defined. Here we demonstrate that NK cells mount a robust, polyfunctional response to WNV characterized by cytolytic activity, cytokine and chemokine secretion. This is associated with downregulation of activating NK cell receptors and upregulation of NK cell activating ligands for NKG2D. The NK cell response did not differ between young and old WNV-naïve subjects, but a history of symptomatic infection is associated with more IFN-γ producing NK cell subsets and a significant decline in a specific NK cell subset. This NK repertoire skewing could either contribute to or follow heightened immune pathogenesis from WNV infection, and suggests that NK cells could play an important role in WNV infection in humans.
Highlights
West Nile virus (WNV) is a mosquito-borne enveloped positive-strand RNA virus belonging to the family Flaviviridae, which includes yellow fever, dengue, and Zika viruses [1, 2]
In response to WNV infection, the frequency of natural killer (NK) cells expressing the chemokine MIP-1β is significantly increased at 8 hours, CD107a is significantly increased at 24 h and 48 h, and IFN-γ is significantly increased at 48 hours post-infection (Fig 1B–1D)
To identify the subsets responding to WNV infection, we considered the maturation state of the NK cells based on expression of CD56, CD16, and CD57 (Fig 1A)
Summary
West Nile virus (WNV) is a mosquito-borne enveloped positive-strand RNA virus belonging to the family Flaviviridae, which includes yellow fever, dengue, and Zika viruses [1, 2]. Since its emergence into the United States in 1999, WNV has spread across North America, South America, and the Caribbean, leading to >41,000 cases in the USA, including 1,753 fatalities [3]. The cumulative incidence of WNV infection may reach 3 million people [1] and no vaccine or targeted antiviral treatment against WNV is available. While the majority of WNV infections are asymptomatic (~80%), some infected patients develop mild symptoms of West Nile fever (~20%), and a small subset (
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