Disease relevance of Plvap

• Poliovirus exists as three stable serotypes (PV-1, PV-2, and PV-3) [1].
• A single amino acid substitution in the capsid proteins VP1 (Thr-22-->Ile) and VP2 (Ser-31-->Thr) identified in the Mah-NK13 and Mah-NL32 genomes, respectively, conferred the mouse-virulent phenotype to the mouse-avirulent PV-1/Mahoney [2].
• Graft microvascular endothelia express an inflamed phenotype associated with wound healing and the repair of tissue damage due to mechanical trauma, ischemia, and/or reperfusion injury--i.e., high levels of ICAM-1 expression and MECA-32 mAb reactivity [3].
• Splenocytes isolated from C3H/HeJ mice infected with coxsackievirus B3 (CVB3) proliferated in vitro not only against a variety of enterovirus (CVB2, CVB3, CVB6, CVA16, PV1) antigens, but against comovirus (CPMV, BPMV) antigens as well [4].

High impact information on Plvap

• These cells express CD31 and the lymphatic lineage markers Prox-1 and Lyve-1, but not the vascular marker MECA-32, and they frequently sprout from preexisting blood vessels [5].
• Compared to the wild-type PV1 (Mahoney) [PV1(M)] sequence, the synthetic virus genome harbored 27 nucleotide (nt) changes deliberately introduced as genetic markers [6].
• Molecular genetic analysis involving recombinants between Mah/I4062M and the LP variants revealed that the mere substitution of an amino acid residue at position 107 in VP1 (Val to Leu) (LP9), position 33 in VP2 (Val to Ile) (LP14), or position 231 in VP3 (Ile to Thr) (LP8) was sufficient to restore the PV1/Mahoney phenotype [7].
• SA virus, a mutant of the Mahoney strain of type 1 poliovirus (PV1/Mahoney), replicates specifically in the spinal cords of mice and causes paralysis, although the PV1/Mahoney strain does not show any mouse neurovirulence (Q. Jia, S. Ohka, K. Iwasaki, K. Tohyama, and A. Nomoto, J. Virol. 73:6041-6047, 1999) [7].
• Mutations were independently introduced into the parental PV-1/Mahoney genome by single-site mutagenesis [2].

Chemical compound and disease context of Plvap

• Because mice can be susceptible to poliovirus infection by parenteral routes, the authors tested the susceptibility to poliovirus-1 (PV-1) of a panel of murine neuronal cell lines differing in their ability to express Prnp [8].

Biological context of Plvap

• To ask whether the antigenic phenotype of maternal endothelial cells (EC) in the vascular zone and central decidua basalis may reflect a specialized programming of these vessels for interaction with the trophoblast, we did a survey of several mouse EC differentiation antigens, including MECA-32, MECA-99, and endoglin [9].
• This differentiation correlates with the downregulation of MECA-32 antigen expression [10].
• Radiation hybrid panel mapping has localized the human and mouse PLVAP genes to chromosomes 19p13.2 and 8B3-C1, respectively [11].
• The genomic organization of the human and mouse genes (HGMW-approved symbol PLVAP) has been determined, and the analysis of their 5' flanking regions has found a highly conserved classical TATA-driven promoter that shows several transcription factor consensus binding sites [11].
• In contrast to the systemic upregulation of ICAM-1 and VCAM-1, cerebral vessels located in the center of the cellular infiltrate started to express the MECA-32 antigen, suggesting an altered functional status of the endothelial cells, as this antigen is suppressed during development of the blood-brain barrier (BBB) [12].

Anatomical context of Plvap

• These data indicate that the PV-1 protein is negatively regulated in pulmonary endothelial cells by VEGF-R2 signaling [13].
• In the Cav-1 null lungs, PV-1 is nearly undetectable in endothelial cells, but remains unchanged in pneumocytes and bronchial epithelial cells [13].
• PV-1 does not fractionate with caveolae on a sucrose density gradient, but the Cav-1 protein is detected in fractions following immunoprecipitation with PV-1 antibodies [13].
• The results suggest that MECA-32 antigen expression is temporally and spatially correlated with the development of the blood brain barrier [10].
• Vessels in the central decidua basalis and the vascular zone showed strong expression of MECA-99 but only weak expression of MECA-32, contrasting with the MECA-99(lo), MECA-32(hi) vessels in the capsularis [9].

Associations of Plvap with chemical compounds

• An N-glycosylated 60-kDa PV-1 protein that binds heparin was detected in mouse lung from a single mRNA transcript [13].
• The conserved extracellular domain features found in rat, mouse, and human PV-1 protein are four N-glycosylation sites, two coiled-coil domains, a proline-rich region, and even cysteine spacing [11].
• The mutation of the adenine residue at position 480 of the 5' noncoding region into a guanine residue has been shown to be an important determinant of PV-1 attenuation in monkeys [14].

Other interactions of Plvap

• PCR analyses of grafts during development of MECA-32 reactivity indicate that cardiac isografts contain mRNA for IL-1, IL-6, TNF, and lymphotoxin [15].
• In spite of expressing several other endothelial markers such as endothelial cell nitrous oxide synthase (ECNOS) and MECA-32, this newly defined population failed to produce endothelial colonies when cultured on OP9 stroma, in direct contrast to enzymatically dissociated VE-cadherin+ cells [16].

Analytical, diagnostic and therapeutic context of Plvap

• Northern blotting of mouse and human tissues is in agreement with and expands those performed in rat and correlated well with the postulated presence of PV-1 in the endothelial diaphragms [11].
• The microvascular endothelia of these cardiac allografts all develop strong reactivity with the monoclonal antibodies (mAbs) YN1.1/74 (anti-ICAM-1), M/K-2 (anti-VCAM-1) and MECA-32 (undefined molecule) within 3 to 5 days of graft implantation [17].
• Preliminary studies demonstrated that cardiac allograft endothelia develop reactivity with MECA-32 monoclonal antibody (MAb) and M/K-2 (anti-VCAM-1) MAb within 3 days of transplantation, whereas cardiac isografts develop MECA-32 reactivity but no M/K-2 reactivity [18].
• We observed that vascular endothelia in both liver isografts and allografts develop reactivity with MECA-32 mAb within two days of transplantation, indicating endothelial activation in both situations [19].
• We have employed a murine model of cardiac transplantation and two monoclonal antibodies, M/K-2 and MECA-32, to study the responses of graft endothelia during allograft rejection [15].

References