Disease relevance of PVRL2

• The expression of PVR and/or Nectin-2 was less frequent in lymphoblastic leukemias [1].
• Analysis of the ligands for triggering NK receptors revealed the consistent expression of Poliovirus receptor (PVR) and Nectin-2 in myeloid leukemias [1].
• A third receptor, HveB (nectin-2), mediates entry of HSV-2 and only a limited number of HSV-1 strains [2].
• Neither PRR1 nor PRR2 binds poliovirus and it is assumed that their physiological functions differ from that of CD155 [3].
• Nectin2alpha (PRR2alpha or HveB) and nectin2delta are low-efficiency mediators for entry of herpes simplex virus mutants carrying the Leu25Pro substitution in glycoprotein D [4].

High impact information on PVRL2

• In the present paper, we show that PVR and Nectin-2 are expressed at cell junctions on primary vascular endothelial cells [5].
• These receptors include the herpesvirus entry mediator (HVEM), nectin-1, nectin-2, and sites in heparan sulfate generated by specific 3-O-sulfotransferases [6].
• The exposure of pDCs to IL-3 increased their susceptibility to NK-cell cytotoxicity resulting from a de novo expression of ligands for activating NK-cell receptors, such as the DNAM-1 ligand nectin-2 [7].
• Overexpression of a truncated form of nectin-2 incapable of interacting with afadin failed to form cell-cell adhesion [8].
• Co-expression of nectin-2 and normal beta-catenin did not form strong cell-cell adhesion [8].

Biological context of PVRL2

• In conclusion, the analysis of a very large data set suggests that genetic polymorphisms in PVRL2 may influence MS severity and supports the possibility that viral factors may contribute to the clinical course of MS, consistent with previous reports [9].
• Mutations in region II, patterned after a reported single-nucleotide polymorphism in nectin-2, enhanced intracellular accumulation of both nectin-1 and nectin-2 and had a deleterious effect on all of the activities under study [10].
• In situ hybridization allowed us to map PRR2 to the 19q13.2-q13.4 bands of the human genome, in the same chromosomal region as PVR [11].
• Amino acid differences at seven positions in the N termini of the glycoproteins D (gDs) specified by herpes simplex virus type 1 (HSV-1) and HSV-2 are largely responsible for the significantly higher cell fusion activity of HSV-2 gD with Chinese hamster ovary cells expressing human nectin-2 or only an endogenous hamster receptor [12].
• Cells transfected with the dynamin 3 construct had less uniformly distributed nectin 2 at intercellular contacts when compared to control cells expressing only nectin 2 or transfected with the DsRed plasmid alone [13].

Anatomical context of PVRL2

• Conversely, FACS analysis and immunostaining demonstrated that extravillous trophoblast cells expressed HveA, HveB, and HveC, and these cells were efficiently infected by HSV vectors [14].
• HveB was expressed in some human neuronal cell lines, fibroblastic cells, keratinocytes, and primary activated T lymphocytes [15].
• Antibodies specific for HveB blocked infection of HveB-expressing CHO cells and a human fibroblastic cell strain HEL299 [15].
• CONCLUSION: The relationship between the PRR2 Sau96I (A/G) polymorphism and early onset coronary artery disease may be due to linkage disequilibrium with the APOE gene and underrepresentation, or a protective effect, of the epsilon2 allele [16].
• Nectin-2(-/-) mice have shown male-specific infertility, disrupted Sertoli-spermatid junctions and morphologically impaired spermatid development [17].

Physical interactions of PVRL2

• Mutations in region I previously shown to severely impair herpes simplex virus (HSV) entry activity, but not pseudorabies virus (PRV) or bovine herpesvirus 1 (BHV-1) entry, did not reduce homotypic trans interactions for either nectin-1 or nectin-2 or binding of nectin-3 to nectin-1 [10].

Other interactions of PVRL2

• Here, we examined relationships between a PRR2 Sau96I (A/G) polymorphism, the epsilon2, 3 and 4 alleles of APOE and CHD [16].
• Susceptibility of the virus-producing target cells to NK cell lysis was partially reversed by blocking ULBP-1 or CD112 with specific antibodies [18].
• Overall, our findings do not support a role of HVEB and PVR genes in the development of MS [19].
• The structures of these three components are discussed, with particular emphasis on the molecular mechanisms by which E-cadherin and nectin-2 promote cell adhesion [20].

Analytical, diagnostic and therapeutic context of PVRL2

• In addition, Northern blot analysis showed that two mRNA isoforms of 3.0 kb (PRR2 alpha) and 4.4 kb (PRR2 delta) are ubiquitously found in various normal human tissues [11].
• Using a degenerate PCR strategy, we describe the identification of a second human PVR-related gene (PRR2), which encodes two glycoproteins, PRR2 alpha (short form) and PRR2 delta (long form) [11].
• We performed fluorescence-activated cell sorting (FACS) analyses and immunostaining to demonstrate that HveA, HveB, and HveC were not expressed in third-trimester villous trophoblast cells [14].

References