Defining the role of NK cells during dengue virus infection

Abstract

In recent years, our understanding of the complex number of signals that need to be integrated between a diverse number of receptors present on natural killer (NK) cells and ligands present on target cells has improved. Here, we review the progress made in identifying interactions between dengue viral peptides presented on HLA Class 1 molecules with inhibitory and activating killer-like immunoglobulin receptors on NK cells, direct interactions of viral proteins with NK cell receptors, the involvement of dengue virus-specific antibodies in mediating antibody-dependent cell-mediated cytotoxicity and the role of soluble factors in modulating NK cell responses. We discuss findings of NK cell activation early after natural dengue infection, and point to the role that NK cells may play in regulating both innate and adaptive immune responses, in the context of our new appreciation of interactions of dengue virus with specific NK cell receptors. With a number of flavivirus vaccine candidates in clinical trials, how NK cells respond to attenuated dengue virus and subunit protein vaccine candidates and shape adaptive immunity will need to be considered.

Glycogen synthetase kinase 3 inhibition drives MIC‐A/B to promote cytokine production by human natural killer cells in Dengue virus type 2 infection

“…This acute phase of infection is accompanied by an early type I IFN response, and the recruitment of immune cells, like mast cells and neutrophils to develop inflammatory responses . This process is followed by the activation of inflammatory monocytes and NK cells, in association with the development of the first clinical symptoms .…”

HLA Upregulation During Dengue Virus Infection Suppresses the Natural Killer Cell Response

“…NK cells can also kill DENV-infected cells in the absence of ADCC (Costa et al, 2017). Several NK cell receptors, namely DNAM-1, NKG2D, and NKp44 have been implicated in this direct recognition of DENV-infected cells (Beltrán and López-Vergès, 2014; Petitdemange et al, 2014; Costa et al, 2017; Mathew, 2018). However, DENV may also evade the NK cell response, most notably through upregulation of HLA class I (Lobigs et al, 1996; Momburg et al, 2001; Hershkovitz et al, 2008; Glasner et al, 2017; Drews et al, 2018).…”

Natural killer cell responses to emerging viruses of zoonotic origin

“…In severe cases (∼1%) facial bleeding and frequent vomiting, blood in vomit and stool. Inhibition of type I IFN responses, upregulation MHC class I [ 96 ] Very Likely . NK cell IFN-γ required for early control [ 89 •• ].…”

“…However, despite a strong IFN response and potent NK cell activation, viral replication can reach high levels in patients and in vitro [ 92 , 93 , 94 , 95 ]. Rather than directly impeding the engagement of NK cell activating receptors, like Ebola, Dengue instead can evade NK cell targeting by upregulating HLA molecules on infected cells [ 96 ]. Indeed, blocking HLA in vitro restores NK cell degranulation against Dengue-infected cells, and NK cell cytotoxicity is diminished at early disease stages when viral titers are highest [ 95 , 97 ].…”