COVID-19 researchGene: PVR
Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): 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 through interaction with other nectins. It is both a viral receptor and immunomodulatory protein and is involved in many biological processes. PVR serves as the entry receptor for poliovirus and thereby is responsible for human susceptibility to poliovirus infection. Susceptibility to poliovirus is a function of the presence or absence of the 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. Evidence for PVR as a Viral Receptor, regulator of immune function and its role in cancer is described in Bowers et al (2017). CD155-deficient mice develop normally without displaying an overt phenotype. However, the animals are distinguished by distinct deficits in the development of a regular humoral immune response (Maier et al, 2007)
PMID: 28870470 - Bowers et al, 2017 (Review) - PVR is an important cell adhesion protein and is involved in the transendothelial migration of leukocytes. PVR undergoes alternative splicing, generating 4 unique splice forms. Protein isoforms and interactions with Poliovirus are summarized in Table 1. In addition to its role as a receptor for the human poliovirus, several native biological functions have also been uncovered. PVR is an important cell adhesion protein and is involved in the transendothelial migration of leukocytes. Through its interactions with CD226 and TIGIT, transmembrane proteins found on leukocytes, PVR is a key regulator of the cell-mediated immune response. In this review more evidence is available for PVR as a Viral Receptor and PVR as a regulator of immune function
PMID: 25113908 - Bolduan et al, 2014 - NL4-3 Vpu protein from HIV downregulates the activating NK cell receptor CD155 from the cell surface by the conserved alanine residues Ala-10, Ala-14 and Ala-18 of its TM domain to evade NK cell mediated immune response against HIV-1 infected cells (Hela cells)
PMID: 19815499 - Stanietsky et al, 2009 - TIGIT (a protein expressed by all human NK cells) binds PVR and PVRL2 but not PVRL3 and inhibits NK cytotoxicity directly through its ITIM.
PMID: 12943679 - Baury et al, 2003 -As the extracellular domains of the sPVR (soluble PVR) isoforms are identical to the extracellular domain of transmembrane PVR, they can compete with transmembrane PVR for the canyon-like receptor binding site of poliovirus. When sPVR is overexpressed in poliovirus susceptible HeLa cells, it significantly reduces viral entry and viral infectivity
PMID: 17621371 - Maier et al, 2007 - In this study, Maier et al explore the expression profile of CD155 on murine hematopoietic cells utilizing newly generated mAb. They report on the establishment and immunological analysis of mice deficient in CD155. CD155-deficient mice (knock out) develop normally without displaying an overt phenotype. However, the animals are distinguished by distinct deficits in the development of a regular humoral immune response. Whereas systemic challenges revealed no differences, orally administered antigen evoked less efficient IgG and IgA antibody responses (Figure 7) despite of normal IgM titers when compared to wild-type mice. Therefore, CD155 may assist in an efficient humoral immune response generated within the intestinal immune system.
PMID: 28800489 - Lin et al, 2017 - Amino acid changes in the C’C”D region in poliovirus receptor domain 1 disrupt poliovirus binding. We substituted this region of Pvr into the corresponding region of a murine homolog, nectin-2. The chimeric receptor, nectin-2Pvr(c'c"d), rendered transformed L cells susceptible to infection with poliovirus P1/Mahoney, but not with polioviruses P2/ Lansing and P3/Leon, due to lack of binding.
PMID: 2597248 - Kanemaru et al, 2015 - Mice genetically deficient in CD155 or treated with anti-CD155 Ab exhibited attenuated Th1-type contact hypersensitivity. Thus, CD155 plays an important regulatory role in helper T cell differentiation and allergic diseases.
Created: 28 May 2020, 3:26 p.m. | Last Modified: 28 May 2020, 3:26 p.m.
Panel Version: 0.349
Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team.
Created: 28 May 2020, 12:36 p.m. | Last Modified: 28 May 2020, 12:36 p.m.
Panel Version: 0.336
gene: PVR was added gene: PVR was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber Mode of inheritance for gene: PVR was set to Unknown