NK cells and poxvirus infection

Abstract

In recent years, our understanding of the role of natural killer (NK) cells in the response to viral infection has grown rapidly. Not only do we realize viruses have many immune-evasion strategies to escape NK cell responses, but that stimulation of NK cell subsets during an antiviral response occurs through receptors seemingly geared directly at viral products and that NK cells can provide a memory response to viral pathogens. Tremendous knowledge has been gained in this area through the study of herpes viruses, but appreciation for the significance of NK cells in the response to other types of viral infections is growing. The function of NK cells in defense against poxviruses has emerged over several decades beginning with the early seminal studies showing the role of NK cells and the NK gene complex in susceptibility of mouse strains to ectromelia, a poxvirus pathogen of mice. More recently, greater understanding has emerged of the molecular details of the response. Given that human diseases caused by poxviruses can be as lethal as smallpox or as benign as Molluscum contagiosum, and that vaccinia virus, the prototypic member of the pox family, persists as a mainstay of vaccine design and has potential as an oncolytic virus for tumor therapy, further research in this area remains important. This review focuses on recent advances in understanding the role of NK cells in the immune response to poxviruses, the receptors involved in activation of NK cells during poxvirus infection, and the viral evasion strategies poxviruses employ to avoid the NK response.

Keywords: MHC class I; NK receptor; NKRP1; Qa-1; ectromelia virus; natural killer cells; poxvirus; vaccinia virus.

FIGURE 1

Human NK cell recognition of vaccinia virus-infected cells. The activating and inhibitory human receptors and ligands are shown for vaccinia virus infection of human cells. The effect of infection on the ligands is indicated with an arrow for molecules that increase and a line to proteins that are reduced.

FIGURE 2

Mouse NK cell recognition of ectromelia virus-infected cells. The activating and inhibitory mouse receptors and ligands are shown for ectromelia virus infection. The effect of infection on the ligands is indicated with an arrow for molecules that increase and a line to proteins that are reduced.