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PVR

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c18h10orf71
Official Full Name
PVR cell adhesion molecule
Organism
Homo sapiens
Gene ID
5817
Background
The protein encoded by this gene is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]
Synonyms
PVS; HVED; CD155; NECL5; TAGE4; Necl-5

Cat.No. Product Name Price
SHH387164 shRNA set against Human PVR (NM_006505.3) Inquiry
SHH387168 shRNA set against Mouse PVR (NM_027514.2) Inquiry
SHR155156 shRNA set against Rat PVR(NM_017076.2) Inquiry
Cat.No. Product Name Price
CDCB156939 Cynomolgus PVR ORF clone Inquiry
MiUTR3H-01785 PVR miRNA 3'UTR clone Inquiry
MiUTR1R-06223 PVR miRNA 3'UTR clone Inquiry
CDFR011143 Rat PVR cDNA Clone(NM_017076.2) Inquiry
CDFH015633 Human PVR cDNA Clone(NM_001135770.1) Inquiry
CDFH015632 Human PVR cDNA Clone(NM_001135768.1) Inquiry
CDFH015631 Human PVR cDNA Clone(NM_001135769.1) Inquiry
CDCS408127 Human PVR ORF Clone (BC015542) Inquiry
MiUTR4H-TG07222 PVR miRNA 3'UTR clone Inquiry
CDCL183196 Rat CD155 ORF clone(NM_017076.2) Inquiry
CDCL183193 Human CD155 ORF clone(NM_006505.3) Inquiry
CDCH395992 Mouse PVR ORF clone(NM_027514.2) Inquiry
CDCH070184 human PVR ORF clone (NM_001135770.1) Inquiry
CDCB157241 Mouse PVR ORF clone (NM_027514.1) Inquiry
SKO0731 PVR Validated sgRNA vector Inquiry
CDCH070182 human PVR ORF clone (NM_001135769.1) Inquiry
CDCB192501 Rabbit C18H10orf71 ORF clone (XM_002718328.2) Inquiry
CDCB181194 Rabbit PVR ORF clone (NM_001171117.1) Inquiry
CDCL183194 Human CD155 ORF clone(NM_001135768.1) Inquiry

Detailed Information

The PVR gene encodes the poliovirus receptor protein, also known as CD155 or nectin-like molecule, a member of the immunoglobulin superfamily. Located on human chromosome 19q13.31, the gene produces a type I transmembrane glycoprotein with an extracellular portion containing three immunoglobulin-like domains, enabling interactions with multiple ligands. PVR is primate-specific and was initially identified for its role as the primary receptor mediating poliovirus entry into host cells. Alternative splicing of PVR produces multiple transcript variants encoding transmembrane and secreted isoforms, increasing its functional complexity. In normal tissues, PVR is broadly expressed in epithelial cells, endothelial cells, and neurons, while expression in immune cells is tightly regulated. Notably, PVR is frequently overexpressed in several human malignancies-including colorectal, lung, pancreatic cancers, and neuroblastoma-where its abnormal expression correlates with tumor progression.

Biological Significance

Beyond its role as a viral receptor, PVR serves as a critical hub connecting innate immunity, tumor immunology, and fundamental cell biology. Immunologically, PVR is a shared ligand for two key receptors on natural killer (NK) cells and T cells: the activating receptor CD226 and the inhibitory receptors TIGIT and CD96. This "yin-yang" ligand identity enables PVR to finely regulate immune synapse formation and lymphocyte effector functions. Interaction with CD226 delivers a strong activating signal, promoting NK and T cell adhesion, cytokine production, and cytotoxic granule release, facilitating the clearance of infected or transformed cells. Conversely, binding to the higher-affinity inhibitory receptor TIGIT transmits negative signals, suppressing immune responses and representing a key mechanism of tumor immune evasion. The PVR-CD226/TIGIT axis therefore, functions as a sophisticated immune checkpoint system, balancing self- versus non-self recognition and attack.

Figure 1. CD155 serves a crucial role in tumor cell invasion, migration, and proliferation.Figure 1. CD155 serves a crucial role in tumor cell invasion, migration, and proliferation. (Liu L, et al., 2021)

PVR also contributes to fundamental cellular processes. Through interaction with the microtubule motor protein light chain Tctex-1/DYNLT1, it participates in microtubule-dependent transport of vesicles and organelles, essential for maintaining cell polarity and axonal transport in neurons. In tumor biology, PVR overexpression not only suppresses antitumor immunity via immune checkpoint mechanisms but also directly enhances tumor cell invasion, migration, and metastasis by promoting adhesion to extracellular matrix proteins such as fibronectin and modulating intracellular signaling pathways. Recent studies have described a "fratricide" phenomenon in which PVR on tumor cell surfaces can transfer to NK cells, potentially causing NK cells to kill each other through self-recognition, further aiding immune escape.

Clinical Relevance

PVR has emerged as a key focus in cancer immunotherapy, particularly as a target in immune checkpoint inhibition strategies. Blocking the PVR-TIGIT axis has become a promising approach to enhance antitumor immunity. Multiple anti-TIGIT monoclonal antibodies are currently in phase II/III clinical trials, either as monotherapy or in combination with anti-PD-1/PD-L1 antibodies, for treating solid tumors such as non-small cell lung cancer and melanoma. These therapies aim to release TIGIT-mediated suppression and restore CD226-driven activation, reactivating T and NK cells to attack tumors.

PVR itself is also considered a direct therapeutic target. Strategies include developing bispecific antibodies or engineered ligands that block PVR-TIGIT interactions while preserving or promoting PVR-CD226 engagement. Its tumor-specific overexpression also makes PVR a promising antigen for chimeric antigen receptor (CAR) T cell and NK cell therapies. However, therapeutic strategies must precisely distinguish its interactions with different receptors to avoid inadvertently blocking activating signals while inhibiting suppressive ones.

In neurobiology, as the only known receptor for poliovirus, PVR's structure and function studies provide critical insights into viral entry and pathogenesis. In transplantation and autoimmune diseases, modulating the PVR-CD226/TIGIT axis may offer new avenues to fine-tune immune responses. Overall, PVR's multifunctional role as an immune regulator highlights its translational potential, particularly for next-generation immune checkpoint therapies, though its complexity necessitates highly precise therapeutic interventions.

References

  1. Zhou R, Chen S, Wu Q, et al. CD155 and its receptors in cancer immune escape and immunotherapy. Cancer Lett. 2023 Oct 1;573:216381.
  2. Liu L, You X, Han S, et al. CD155/TIGIT, a novel immune checkpoint in human cancers (Review). Oncol Rep. 2021 Mar;45(3):835-845.
  3. Deuss FA, Gully BS, Rossjohn J, et al. Recognition of nectin-like protein-5 by the immune receptor TIGIT. J Biol Chem. 2017;292(27):11413–11422.
  4. Gao J, Zheng Q, Xin N, et al. CD155, an onco-immunologic molecule in human tumors. Cancer Sci. 2017;108(10):1934–1938.
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