CD155

CD155
Name	CD155
Alt	Poliovirus receptor
Uniprot	P15151
Genes	PVR
Organism	Human
Length	~345 aa (isoforms vary)

CD155 is a transmembrane glycoprotein originally identified as the cellular receptor for poliovirus. It is encoded by the PVR gene and is expressed broadly on human epithelial cells, endothelial cells, and some hematopoietic cells. CD155 participates in cell adhesion, migration, and signaling and has been implicated in viral infection, tumor immunology, and immune regulation. The protein interacts with several immune receptors and extracellular matrix components, positioning it at the interface of host defense and tissue homeostasis.

Structure and Expression

CD155 is a member of the nectin-like family and comprises an extracellular region containing three immunoglobulin-like (Ig-like) domains, a single-pass transmembrane helix, and a cytoplasmic tail that can be short or extended depending on alternative splicing. The extracellular Ig-like domains mediate interactions with viral capsids and cellular ligands, while the cytoplasmic tail binds intracellular adapters that link to the actin cytoskeleton. CD155 isoforms include transmembrane and soluble forms produced via alternative splicing and proteolytic shedding.

Expression of CD155 is constitutive but regulated: it is upregulated by cellular stressors such as DNA damage, oncogenic signaling, and inflammatory cytokines. Tissues with notable expression include respiratory epithelium, intestinal mucosa, and vascular endothelium. Expression patterns have been documented in studies involving primary human tissues and cell lines originating from organs such as the lung, colon, and skin, as well as in cultured endothelial cells derived from the heart and brain.

Function and Mechanisms

At the molecular level, CD155 functions as a cell adhesion molecule that modulates intercellular junctions and cell motility. Through its extracellular domains, CD155 interacts with extracellular matrix components and neighboring cell-surface molecules to influence cell polarity and migration. Intracellularly, CD155 engages adaptors that regulate actin dynamics, contributing to directed cell movement and wound-healing responses observed in vitro and in vivo.

CD155 also forms cis- and trans-interactions with other nectin family members and adhesion proteins, affecting junctional complexes at cell–cell contacts. Signaling downstream of CD155 can alter phosphorylation cascades and small GTPase activity, thereby integrating signals from growth factor receptors and stress-activated pathways. These mechanistic features explain CD155’s involvement in processes such as tissue remodeling, angiogenesis, and epithelial barrier modulation.

Role in Immune Regulation

CD155 serves as a ligand for several immune receptors expressed by lymphoid cells, modulating innate and adaptive immune responses. Notably, CD155 binds the activating receptor DNAM-1 (also known as CD226) on natural killer cells and cytotoxic T lymphocytes, promoting cytolytic activity against target cells displaying elevated CD155. Conversely, CD155 also engages inhibitory receptors such as TIGIT and CD96, which can dampen immune effector functions upon binding.

The balance of signals delivered through DNAM-1, TIGIT, and CD96 influences immune surveillance, tolerance, and exhaustion phenotypes in settings such as viral infection and cancer. CD155 expression on antigen-presenting cells and nonhematopoietic stromal cells shapes interactions with T cells and NK cells within lymphoid organs, tumor microenvironments, and sites of inflammation. Regulatory cytokines and checkpoint pathways modulate CD155–receptor interactions, integrating with pathways studied in research involving cytokines like interferons and therapies targeting immune checkpoints.

Involvement in Viral Entry and Pathogenesis

CD155 was first characterized as the receptor for poliovirus, mediating viral attachment and entry into susceptible cells. The Ig-like domains of CD155 bind polioviral capsid proteins, facilitating endocytosis and uncoating. Beyond poliovirus, CD155 can influence susceptibility to other pathogens that exploit related entry routes or that modify CD155 expression indirectly through host response pathways.

Viral modulation of CD155 expression and trafficking affects viral tropism and pathogenesis. For example, some viruses induce upregulation of CD155 as part of stress or interferon responses, thereby altering interactions with immune cells. Historical studies on poliomyelitis and contemporary work on viral-host receptor dynamics have leveraged knowledge of CD155 to understand neurotropism, viral spread within tissues, and host-range determinants.

Implications in Cancer and Therapeutics

CD155 is frequently overexpressed in a variety of malignancies, including carcinomas of the lung, colon, breast, and melanoma, where its elevated presence correlates with tumor cell migration, invasion, and poor prognosis in some cohorts. Overexpression can enhance tumor cell motility via interactions with the cytoskeleton and promote escape from immune surveillance by engaging inhibitory receptors on tumor-infiltrating lymphocytes.

Therapeutic strategies targeting CD155 pathways are under investigation, including blockade of inhibitory receptor interactions (for example, targeting TIGIT), enhancement of DNAM-1–mediated cytotoxicity, and engineered oncolytic viruses that exploit CD155 for selective entry into tumor cells. CD155’s role in antibody-dependent cellular cytotoxicity and checkpoint modulation makes it a candidate biomarker for responses to immunotherapies being tested in clinical studies conducted by academic centers and biotechnology companies.

Genetic Variants and Clinical Associations

Germline and somatic alterations affecting the PVR locus can influence CD155 expression or function. Single-nucleotide polymorphisms and regulatory variants within the PVR gene have been examined for associations with susceptibility to infectious disease and cancer outcomes in population studies. Somatic upregulation or copy-number changes in tumors can contribute to the tumor immune landscape and have been profiled in genomic consortia and sequencing initiatives.

Clinically, altered CD155 expression has been correlated with disease progression markers and therapeutic response parameters in cohorts from oncology trials and epidemiological studies. Functional variants that affect splicing or shedding may modify receptor–ligand interactions and thereby influence immune surveillance or viral entry phenotypes documented in translational research.

Category:Human proteins