Alternative titles; symbols
HGNC Approved Gene Symbol: PVR
Cytogenetic location: 19q13.31 Genomic coordinates (GRCh38): 19:44,643,910-44,666,162 (from NCBI)
PVR, or CD155, belongs to a large family of immunoglobulin (Ig)-like molecules called nectins and nectin-like proteins, which mediate cell-cell adhesion, cell migration, and cell polarization by homotypic contact or heterotypic interaction with other nectins. In addition, PVR serves as the entry receptor for poliovirus and thereby mediates human susceptibility to poliovirus infection (summary by Fuchs et al., 2004).
Primates are susceptible to poliomyelitis infection, but rodents are not; furthermore, human cells but not rodent cells are killed by poliovirus in vitro. Susceptibility to poliovirus is a function of the presence or absence of a cellular receptor to which the virus binds as the first step in poliovirus replication. Mendelsohn et al. (1986) succeeded in transforming a human poliovirus receptor gene into mouse L cells, which are ordinarily resistant to poliovirus infection because they do not bear a poliovirus receptor. Monoclonal antibody directed against the HeLa cell poliovirus receptor site was used in rosette assays to identify poliovirus-sensitive transformants.
Mendelsohn et al. (1989) and Koike et al. (1990) isolated genomic and complementary DNAs for human poliovirus receptors (PVRs) from HeLa cells. Four mRNA isoforms, 2 membrane-bound and 2 secreted, were identified and shown to be generated by alternative splicing from the primary transcript. The PVRs are members of the immunoglobulin superfamily.
Shepley et al. (1988) prepared a monoclonal antibody that identified a 100-kD membrane protein in HeLa cells and in human spinal cord involved in poliovirus attachment. They showed that the antigen identified by the monoclonal antibody was associated with the presence of human chromosome 19 in human-mouse hybrid cell lines. The monoclonal antibodies stained neurons in the reticular formation and clusters of brainstem neurons, consistent with the known pattern of damage caused by poliovirus infection in the brainstem. Furthermore, it reacted with human peripheral mononuclear cells, consistent with the known replication of poliovirus in Peyer patches and tonsils.
By analysis of transgenic mice expressing human CD155, Gromeier et al. (2000) observed expression of CD155 within embryonic structures giving rise to spinal cord anterior horn motor neurons. They suggested that this expression may explain the restrictive host cell tropism of poliovirus for this cellular compartment of the central nervous system.
Solecki et al. (2002) noted that CD155 is aberrantly expressed in neuroectodermal tumors. RT-PCR analysis showed that SHH (600725) treatment of teratocarcinoma cells upregulates CDC155 and that this upregulation requires an intact GLI (165220)-binding site. The authors proposed that their finding might help explain the normal function of CD155 during development and its expression in tumors.
Bottino et al. (2003) immunized mice with natural killer (NK)-susceptible human target cells and obtained antibodies to PVR and nectin-2 (PVRL2; 600798). Binding analysis and flow cytometry demonstrated that both molecules bound strongly with DNAM1 (CD226; 605397), but not with other activating NK receptors, including NKp46 (NCR1; 604530) and NKp30 (NCR3; 611550). Expression of PVR or PVRL2 rendered cells susceptible to enhanced lysis in a DNAM1-dependent manner that was nearly abrogated in the presence of antibody to PVR, PVRL2, or DNAM1.
Using flow cytometric analysis and fluorescence microscopy, Fuchs et al. (2004) demonstrated that NK cells recognize PVR through an additional receptor, CD96 (606037). CD96 promoted NK cell adhesion to target cells expressing PVR, stimulated cytotoxicity by activated NK cells, and mediated acquisition of PVR from target cells.
By flow cytometric and immunohistochemical analysis, Reymond et al. (2004) found that PVR and nectin-2 were expressed at cell junctions on primary vascular endothelial cells. Binding of DNAM1 at endothelial junctions was abrogated by anti-PVR, but not by anti-nectin-2. Transmigration assays showed that either anti-PVR or anti-DNAM1 blocked monocyte transmigration through endothelium, with monocyte arrest at the apical surface of endothelium over intercellular junctions, suggesting that the DNAM1-PVR interaction occurs during diapedesis. Reymond et al. (2004) concluded that DNAM1 regulates monocyte extravasation via interaction with PVR.
Tomasec et al. (2005) showed that cells infected with high-passage cytomegalovirus (CMV) strains were more susceptible to NK cell-mediated lysis than cells infected with low-passage CMV strains. They determined that high-passage CMV strains, such as AD169, had spontaneous 13- to 15-kb deletions that included the UL141 gene product. Tomasec et al. (2005) found that UL141 mediated efficient protection against a wide range of NK populations by downregulating expression of CD155 on the NK cell surface.
Crystal Structure
He et al. (2000) determined the structure of the extracellular, 3-domain PVR/CD155 molecule complexed with poliovirus at 22-angstrom resolution.
In a study of human-mouse hybrids, Miller et al. (1974) showed that chromosome 19 is correlated with susceptibility to poliovirus. Siddique et al. (1985) regionalized the PVS gene to 19q13-qter. By the study of rodent/human hybrid cell lines carrying 4 different regions of human chromosome 19, Siddique et al. (1988) demonstrated that the typical cytopathic effects of poliovirus infection were observed only when the region 19q12-q13.2 was contained as the smallest region of overlap. The same region contains the gene for myotonic dystrophy (160900). The PVS gene is also of interest in connection with inherited motor neuron diseases because it encodes a cell-surface receptor expressed on motor neurons.
Schonk et al. (1990) assigned the PVS gene to 19q13.2 by hybridization studies using a panel of somatic cell hybrids with subchromosomal segments of 19q. By fluorescence in situ hybridization, Trask et al. (1993) assigned the PVS gene to 19q13.2-q13.3. Seldin et al. (1991) mapped the homologous gene in the mouse to chromosome 9.
Koike et al. (1991) noted that mouse L cells are not permissive for poliovirus infection. However, mouse L-cell transformants carrying the human PVS gene are permissive for infection of all 3 serotypes of poliovirus. This observation indicated that all 3 serotypes use the same cellular receptor and that mouse cells have the cellular machinery for poliovirus replication except for the receptor. Koike et al. (1991) created transgenic mice carrying the human PVS gene. They demonstrated sensitivity of the cells in the central nervous system of the transgenic mice to poliovirus and suggested that the transgenic mice may be an excellent animal model for studying the pathogenesis of polio and assessing poliovirus vaccines.
Bottino, C., Castriconi, R., Pende, D., Rivera, P., Nanni, M., Carnemolla, B., Cantoni, C., Grassi, J., Marcenaro, S., Reymond, N., Vitale, M., Moretta, L., Lopez, M., Moretta, A. Identification of PVR (CD155) and nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J. Exp. Med. 198: 557-567, 2003. [PubMed: 12913096] [Full Text: https://doi.org/10.1084/jem.20030788]
Fuchs, A., Cella, M., Giurisato, E., Shaw, A. S., Colonna, M. Cutting edge: CD96 (tactile) promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155). J. Immun. 172: 3994-3998, 2004. [PubMed: 15034010] [Full Text: https://doi.org/10.4049/jimmunol.172.7.3994]
Gromeier, M., Solecki, D., Patel, D. D., Wimmer, E. Expression of the human poliovirus receptor/CD155 gene during development of the central nervous system: implications for the pathogenesis of poliomyelitis. Virology 273: 248-257, 2000. [PubMed: 10915595] [Full Text: https://doi.org/10.1006/viro.2000.0418]
He, Y., Bowman, V. D., Mueller, S., Bator, C. M., Bella, J., Peng, X., Baker, T. S., Wimmer, E., Kuhn, R. J., Rossmann, M. G. Interaction of the poliovirus receptor with poliovirus. Proc. Nat. Acad. Sci. 97: 79-84, 2000. [PubMed: 10618374] [Full Text: https://doi.org/10.1073/pnas.97.1.79]
Koike, S., Horie, H., Ise, I., Okitsu, A., Yoshida, M., Iizuka, N., Takeuchi, K., Takegami, T., Nomoto, A. The poliovirus receptor protein is produced both as membrane-bound and secreted forms. EMBO J. 9: 3217-3224, 1990. [PubMed: 2170108] [Full Text: https://doi.org/10.1002/j.1460-2075.1990.tb07520.x]
Koike, S., Taya, C., Kurata, T., Abe, S., Ise, I., Yonekawa, H., Nomoto, A. Transgenic mice susceptible to poliovirus. Proc. Nat. Acad. Sci. 88: 951-955, 1991. [PubMed: 1846972] [Full Text: https://doi.org/10.1073/pnas.88.3.951]
Mendelsohn, C., Johnson, B., Lionetti, K. A., Nobis, P., Wimmer, E., Racaniello, V. R. Transformation of a human poliovirus receptor gene into mouse cells. Proc. Nat. Acad. Sci. 83: 7845-7849, 1986. [PubMed: 3020560] [Full Text: https://doi.org/10.1073/pnas.83.20.7845]
Mendelsohn, C. L., Wimmer, E., Racaniello, V. R. Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell 56: 855-865, 1989. [PubMed: 2538245] [Full Text: https://doi.org/10.1016/0092-8674(89)90690-9]
Miller, D. A., Miller, O. J., Dev, V. G., Hashmi, S., Tantravahi, R. R., Medrano, L., Green, H. Human chromosome 19 carries a poliovirus receptor gene. Cell 1: 167-174, 1974.
Reymond, N., Imbert, A.-M., Devilard, E., Fabre, S., Chabannon, C., Xerri, L., Farnarier, C., Cantoni, C., Bottino, C., Moretta, A., Dubreuil, P., Lopez, M. DNAM-1 and PVR regulate monocyte migration through endothelial junctions. J. Exp. Med. 199: 1331-1341, 2004. [PubMed: 15136589] [Full Text: https://doi.org/10.1084/jem.20032206]
Schonk, D., van Dijk, P., Riegmann, P., Trapman, J., Holm, C., Willcocks, T. C., Sillekens, P., van Venrooij, W., Wimmer, E., Geurts van Kessel, A., Ropers, H.-H., Wieringa, B. Assignment of seven genes to distinct intervals on the midportion of human chromosome 19q surrounding the myotonic dystrophy gene region. Cytogenet. Cell Genet. 54: 15-19, 1990. [PubMed: 1701111] [Full Text: https://doi.org/10.1159/000132946]
Seldin, M. F., Saunders, A. M., Rochelle, J. M., Howard, T. A. A proximal mouse chromosome 9 linkage map that further defines linkage groups homologous with segments of human chromosomes 11, 15, and 19. Genomics 9: 678-685, 1991. [PubMed: 1674729] [Full Text: https://doi.org/10.1016/0888-7543(91)90361-h]
Shepley, M. P., Sherry, B., Weiner, H. L. Monoclonal antibody identification of a 100-kDa membrane protein in HeLa cells and human spinal cord involved in poliovirus attachment. Proc. Nat. Acad. Sci. 85: 7743-7747, 1988. [PubMed: 2845419] [Full Text: https://doi.org/10.1073/pnas.85.20.7743]
Siddique, T., Bartlett, R. J., McKinney, R., Hung, W.-Y., Bruns, G., Wilfert, C., Roses, A. D. The poliovirus sensitivity (PVS) is on chromosome 19q13-qter. (Abstract) Cytogenet. Cell Genet. 40: 745 only, 1985.
Siddique, T., McKinney, R., Hung, W.-Y., Bartlett, R. J., Bruns, G., Mohandas, T. K., Ropers, H.-H., Wilfert, C., Roses, A. D. The poliovirus sensitivity (PVS) gene is on chromosome 19q12-q13.2. Genomics 3: 156-160, 1988. [PubMed: 2852161] [Full Text: https://doi.org/10.1016/0888-7543(88)90147-4]
Solecki, D. J., Gromeier, M., Mueller, S., Bernhardt, G., Wimmer, E. Expression of the human poliovirus receptor/CD155 gene is activated by Sonic hedgehog. J. Biol. Chem. 277: 25697-25702, 2002. [PubMed: 11983699] [Full Text: https://doi.org/10.1074/jbc.M201378200]
Tomasec, P., Wang, E. C. Y., Davison, A. J., Vojtesek, B., Armstrong, M., Griffin, C., McSharry, B. P., Morris, R. J., Llewellyn-Lacey, S., Rickards, C., Nomoto, A., Sinzger, C., Wilkinson, G. W. G. Downregulation of natural killer cell-activating ligand CD155 by human cytomegalovirus UL141. Nature Immun. 6: 181-188, 2005. [PubMed: 15640804] [Full Text: https://doi.org/10.1038/ni1156]
Trask, B., Fertitta, A., Christensen, M., Youngblom, J., Bergmann, A., Copeland, A., de Jong, P., Mohrenweiser, H., Olsen, A., Carrano, A., Tynan, K. Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers. Genomics 15: 133-145, 1993. [PubMed: 8432525] [Full Text: https://doi.org/10.1006/geno.1993.1021]