The natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection

• Published in: PloS one Vol. 12; no. 2; p. e0172625
• Main Authors: Yao, Yi, Strauss-Albee, Dara M., Zhou, Julian Q., Malawista, Anna, Garcia, Melissa N., Murray, Kristy O., Blish, Catherine A., Montgomery, Ruth R.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.02.2017; Public Library of Science (PLoS)
• Subjects: Adult; Age Factors; Aged; Aged, 80 and over; Antigens, CD - genetics; Antigens, CD - immunology; Antiviral agents; Asymptomatic Diseases; Asymptomatic infection; Biology and life sciences; Care and treatment; Cytokines; Cytolytic activity; Cytomegalovirus; Encephalitis; Epidemics; Female; Gene Expression Regulation; Geriatrics; Health aspects; Hepatitis; Humans; Immunity, Innate; Immunology; Immunophenotyping; Infections; Influenza; Interferon-gamma - genetics; Interferon-gamma - immunology; Internal medicine; Invasiveness; Killer cells; Killer Cells, Natural - immunology; Killer Cells, Natural - virology; Lymphocyte Activation; Lymphocyte Count; Medicine; Medicine and health sciences; Middle Aged; Natural Cytotoxicity Triggering Receptor 1 - genetics; Natural Cytotoxicity Triggering Receptor 1 - immunology; Natural Cytotoxicity Triggering Receptor 2 - genetics; Natural Cytotoxicity Triggering Receptor 2 - immunology; Natural Cytotoxicity Triggering Receptor 3 - genetics; Natural Cytotoxicity Triggering Receptor 3 - immunology; Natural killer cells; NK Cell Lectin-Like Receptor Subfamily C - genetics; NK Cell Lectin-Like Receptor Subfamily C - immunology; NK Cell Lectin-Like Receptor Subfamily K - genetics; NK Cell Lectin-Like Receptor Subfamily K - immunology; NKG2 antigen; Older people; Pathogenesis; Pediatrics; Primary Cell Culture; Receptors; Research and Analysis Methods; Severity of Illness Index; Vector-borne diseases; Viral infections; Virology; Viruses; West Nile fever; West Nile Fever - diagnosis; West Nile Fever - genetics; West Nile Fever - immunology; West Nile Fever - virology; West Nile virus; West Nile virus - growth & development; West Nile virus - immunology; γ-Interferon; United States; California; United States > US; Texas; Connecticut
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0172625

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.