Poliovirus Receptor: More than a simple viral receptor

Abstract

The human poliovirus receptor (PVR) is a cell surface protein with a multitude of functions in human biology. PVR was initially identified as the receptor for the human poliovirus and recent discoveries have given a greater insight into both its morphology and its function. Alternative splicing of the PVR gene results in a total of 4 alternatively spliced isoforms. Two of these isoforms lack a complete transmembrane domain and are considered soluble and block viral infection; the remaining two transmembrane isoforms differ only at their extreme C-terminal domains resulting in differential localization in epithelia and polarity of viral infection. In addition to its role as a receptor for the human poliovirus, several native biological functions have also been uncovered. PVR is an important cell adhesion protein and is involved in the transendothelial migration of leukocytes. Through its interactions with CD226 and TIGIT, transmembrane proteins found on leukocytes, PVR is a key regulator of the cell-mediated immune response. As PVR is differentially regulated in a broad spectrum of cancers, it has a strong potential for clinical use as a biomarker. PVR is also a possible target for novel cancer therapies. Utilizing its natural tropism for PVR, a genetically modified form of the live attenuated poliovirus vaccine is currently being tested for its ability to locate and destroy certain tumors. These recent studies emphasize the importance of PVR in human biology and demonstrate its utility beyond being a viral receptor protein.

NK Cell-Based Immune Checkpoint Inhibition

“…CD155 is a transmembrane glycoprotein, also known as poliovirus receptor (PVR) as it was first identified as a poliovirus entry receptor. PVR (CD155) is a member of the immunoglobulin superfamily as well as being the fifth member of the nectin-like molecule family and is therefore also known as necl-5 (152). It is barely expressed in normal human tissues, but many tumor cell lines and primary malignancies highly express PVR (54,153).…”

CD155: A Multi-Functional Molecule in Tumor Progression

“…CD155 is an immunoglobulin superfamily adhesion molecule involved in many different physiological processes ranging from cell adhesion and migration, proliferation and modulation of immune responses [1][2][3]. Based on its ability to mediate the binding of human poliovirus, CD155 was initially identified as PolioVirus Receptor (PVR) [4].…”

“…In particular, only the cytoplasmic domain of CD155α interacts with the µ1B subunit of the clathrin adaptor complex, directing the sorting of CD155α to basolateral membranes in epithelial cells [14]. Moreover, the CD155α isoform contains an Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) responsible for signal transduction [3]. Upon antibody-mediated CD155 engagement, the ITIM motif is phosphorylated by the c-Src tyrosine kinase allowing the recruitment of the Src homology region 2 domain-containing phosphatase (SHP-2) that initiates intracellular signals [3,15].…”

Targeting PVR (CD155) and its receptors in anti-tumor therapy

“…It interacts with the (co)stimulatory receptor DNAM-1 and the inhibitory receptors TIGIT and CD96, resulting in either immune cell activation or inhibition, respectively. 11 In healthy individuals, the balance between activating and inhibitory signals maintains the normal function of immune cells. However, since this balance is often disturbed in the tumor microenvironment and accumulating data suggest that PVR overexpression induces the immune escape of tumor cells, strategies targeting PVR might direct the immune response toward the elimination of tumor cells.…”

“…However, since this balance is often disturbed in the tumor microenvironment and accumulating data suggest that PVR overexpression induces the immune escape of tumor cells, strategies targeting PVR might direct the immune response toward the elimination of tumor cells. 6,[11][12][13][14][15] Based on these findings, several different approaches based on PVR and its interactions are being explored in the field of antitumor therapy and are described in this review.…”