Disease relevance of Pvr

• Furthermore, Tage4 mRNA was detected in a series of mouse intestinal adenomas by in situ hybridization [1].
• Because altered particles are believed to be an intermediate in poliovirus entry, these findings suggest that Pvr domains 2 and 3 participate in early stages of infection [2].
• Although the initial site of poliovirus replication in humans is the intestine, previously isolated transgenic mice which carry the human poliovirus receptor (PVR) gene (TgPVR mice), which develop poliomyelitis after intracerebral inoculation, are not susceptible to infection by the oral route [3].
• This region is homologous to the human immunodeficiency virus binding region of CD4 and to the poliovirus binding region of CD155 [4].
• In a heterologous coculture system with CD155 expressing mouse neuroblastoma cells, HeLa cell-expressed nectin-3 was recruited to contact sites with CD155 bearing neurites [5].

High impact information on Pvr

• Transgenic mice expressing a human poliovirus receptor: a new model for poliomyelitis [6].
• Transgenic mice expressing human PVR should be useful for studying poliovirus neurovirulence, attenuation, and tissue tropism, and for development and testing of poliovirus vaccine strains [6].
• A human poliovirus receptor (PVR) gene was used to generate transgenic mice that express PVR transcripts and poliovirus binding sites in a wide range of tissues [6].
• Intracerebral inoculation of PVR transgenic mice with poliovirus type 1, Mahoney strain, resulted in viral replication in the brain and spinal cord and development of paralytic poliomyelitis [6].
• Downregulation of natural killer cell-activating ligand CD155 by human cytomegalovirus UL141 [7].

Chemical compound and disease context of Pvr

• BACKGROUND AND AIMS: The Tage4 gene (tumour associated glycoprotein E4) is overexpressed in rat colon tumours and Min mouse intestinal adenomas [8].
• The NH2-terminal immunoglobulin-like domain, domain 1, of the second monkey PVR, which lacks a putative N-glycosylation site, mediated poliovirus infection [9].
• The corresponding Tage4 gene (tumor-associated glycoprotein E4) is also expressed in rat colon tumors induced by 1,2-dimethylhydrazine and in Min mouse intestinal adenomas [10].
• The study revealed that high molecular polyvinyl sulfate (PVP) or sulfonate (PVS), and low molecular alkyldisulfonates (NaO3S(CH2)nSO3Na, n = 2--5: EDS, TDS, BDS and PDS) can alleviate acute toxicity of the herbicide, paraquat dichloride (PQ) in mice [11].

Biological context of Pvr

• We examined here whether Tage4, which was originally identified to be a gene overexpressed in colon carcinoma and has a domain structure similar to those of nectins, is involved in cell adhesion and/or migration [12].
• Thus, Tage4 heterophilically trans-interacts with nectin-3 and regulates cell migration [12].
• Cloning of the corresponding Tage4 cDNA has revealed that this protein contains the conserved amino acids characteristic of members of the immunoglobulin gene superfamily [1].
• Previous work has shown that the first immunoglobulin-like domain of the Pvr protein contains the virus binding site [2].
• To further identify sequences of Pvr important for its interaction with poliovirus, stable cell lines expressing mutated Pvr molecules were examined for their abilities to bind virus and support virus replication [2].

Anatomical context of Pvr

• The cPVR mice express Pvr in a variety of tissues (including small intestines, brain, spinal cord, muscle, blood and liver) and are susceptible to infection after intraperitoneal, intracerebral or intramuscular inoculation of poliovirus [13].
• The poliovirus receptor CD155 and its family member CD112 (nectin-2) are the ligands for the activating cell-surface receptor DNAM-1 on CD8+ T cells and natural killer (NK) cells [14].
• Expression of the poliovirus receptor in intestinal epithelial cells is not sufficient to permit poliovirus replication in the mouse gut [3].
• Upon oral inoculation with poliovirus, no increase in virus titer was detected in the feces of TgFABP-PVR mice, and no virus replication was observed in the small intestine, although poliovirus replicated in the brain after intracerebral inoculation [3].
• Pvr was detected by immunohistochemistry in the enterocytes and M cells of transgenic mouse (TgFABP-PVR) small intestine [3].

Associations of Pvr with chemical compounds

• Nectin-like molecule-5/Tage4 enhances cell migration in an integrin-dependent, Nectin-3-independent manner [15].
• Poliovirus receptor (PVR) is a cell surface glycoprotein that belongs to the immunoglobulin superfamily [16].
• To confirm that mutant PVRs reached the cell surface, an immunological tag, consisting of part of CH3 from human immunoglobulin G1, was engineered into the PVR [17].

Regulatory relationships of Pvr

• We have found that Ig-like Necl-5/Tage4 is up-regulated in NIH3T3 cells transformed by an oncogenic Ras (V12Ras-NIH3T3 cells) and heterophilically trans-interacts with a Ca(2+)-independent Ig-like cell adhesion molecule nectin-3, eventually enhancing their intercellular motility [15].

Other interactions of Pvr

• Here, we analyze expression of the mouse Tage4 gene in Min mouse intestinal adenomas [1].
• Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor [14].
• Mouse cells do not bind poliovirus but express a Pvr homolog, Mph, that does not function as a poliovirus receptor [2].
• The members of the nectin/CD155 gene family represent a growing class of novel cell adhesion molecules of the immunoglobulin superfamily [18].
• Thus, like other virus receptors in the immunoglobulin superfamily, including CD4, poliovirus receptor, and intercellular adhesion molecule 1, the N-terminal domain of MHV receptor is recognized by the virus and the blocking monoclonal antibody [19].

Analytical, diagnostic and therapeutic context of Pvr

• Molecular cloning and expression of a murine homolog of the human poliovirus receptor gene [20].
• METHODS: Overall CD155 expression was assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analysis using tissue specimens from patients with colorectal adenomas and adenocarcinomas [8].
• The newly developed Tg PVR mouse-protection test may be useful in evaluating existing IPV potency tests and for attempts to improve formulations of trivalent IPV or combined vaccines for childhood immunization schedules [21].
• Abundance of PVR RNA is on average three-fold higher in TGM-PRG-3 relative to TGM-PRG-1 tissues, and the abundance of the receptor molecule is three-fold higher in TGM-PRG-3 central nervous system tissues compared to TGM-PRG-1 tissues as determined by Western blot analysis [22].

References