Disease relevance of CPVL

• CPVL did not display enhanced expression in sarcoidosis, vs. TB patients, as observed with angiotensin-converting enzyme (ACE), a related molecule [1].
• These very preterm infants are at highest risk for cerebral hypoxia/ischemia (H/I), intracranial hemorrhage (ICH), periventricular leukomalacia (PVL) or cystic PVL (CPVL), and possible sequelae, cerebral palsy (CP) and mental retardation (MR) [2].
• HPV16 VLP-specific IgGs were consistently detected in all women (n = 11) who were persistently HPV16 DNA positive during follow-up and whose disease ultimately progressed to CIN III (histologically diagnosed severe dysplasia or carcinoma in situ) [3].
• VLP, tentatively considered an aberrant form of type-C particles, were presumably of murine origin since they were not observed in the osteosarcoma cells before passage through NIH nude mice [4].
• Morphologically distinct virus-like particles (VLP), similar to R-type VLP, were observed by electron microscopy in experimental rat central nervous system tumors induced with the B-77-C strain of avian sarcoma virus (ASV) [5].

Psychiatry related information on CPVL

• BACKGROUND: The aim of this study was to evaluate the efficacy of divalproex (VLP) to prevent episode recurrence in postpartum women with bipolar disorder [6].
• Of the 12 patients free of symptoms such as itching, burning and dyspareunia, but with clinical vulval lesions, 11 (92%) had histological confirmation of VLP [7].

High impact information on CPVL

• In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets [8].
• CONCLUSION: HPV16 VLP-specific IgG responses are present in the plasma of a majority of patients with persistent HPV16 infections and histologically confirmed high-grade lesions but only in a smaller subset of patients with cleared HPV16 infections and either normal cervical histology or low-grade CIN lesions [3].
• R-type VLP have a characteristic internal radial structure and were observed previously only in hamster cells and in an established bovine cell line [5].
• Efficient targeting of T cell ligands to lipid rafts and ultimately to VLP is achieved by C-terminal introduction of glycosyl phosphatidyl inositol acceptor sequences, replacing transmembrane and intracellular domains [9].
• VLP expressing the glycoprotein epitope 33-41 of the lymphocytic choriomeningitis virus in the context of H-2D(b) activate and expand naïve, antigen-specific CD8(+) T lymphocytes and differentiate them into cytotoxic effector cells [9].

Chemical compound and disease context of CPVL

• We have investigated the effects of triacsin C, an inhibitor of long chain acyl-CoA synthetase, on release of HIV Gag virus-like particle (VLP) produced using the recombinant baculovirus system [10].
• SC-58125, a structural analog of the Cox-2-selective inhibitor Celebrex reduced by approximately 70% human memory B cell differentiation to HPV 16 VLP IgG-secreting cells [11].
• Additionally, our results demonstrate that, in the absence of Polybrene, initial attachments of non-infectious, envelope protein-free VLP and probably mature infectious virus particles are mediated by interactions of the virus particles with cell surface heparan sulfate, and possibly with other GAG molecules [12].
• To address this, alanine-scanning mutagenesis of BLV PrGag was done with a virus-like particle (VLP) system [13].
• The hapten nicotine was coupled to virus-like particles (VLP) formed by the coat protein of the bacteriophage Qb [14].

Biological context of CPVL

• Possible functions for CPVL in macrophages include digestion of phagocytosed particles in the lysosome, participation in an inflammatory protease cascade, and trimming of peptides for antigen presentation [15].
• The CPVL gene contains at least 13 exons spread over more than 150 kb on human chromosome 7p14-p15 [15].
• CPVL is highly expressed in lamellipodia and membrane ruffles, which also concentrate markers of the secretory pathway (MIP-1alpha and tumour necrosis factor-alpha) and major histocompatibility complex (MHC) class I and II molecules [16].
• Conversely, VLP uptake by Langerhans cells leads to cross-presentation in the absence of costimulation [17].
• Because protection from experimental infection by papillomavirus is mediated by neutralizing IgG, we sought the mechanisms that trigger humoral immunity to HPV16 L1 VLP [18].

Anatomical context of CPVL

• CPVL protein expression was induced during maturation of monocytes into macrophages [15].
• In addition to monocyte/macrophage-rich sources such as spleen, leukocytes, and placenta, CPVL mRNA is abundantly expressed in heart and kidney, suggesting a separate role for CPVL outside the immune system [15].
• Initial studies suggested that CPVL is largely restricted to the monocytic lineage, although it may also be expressed by cells outside the immune system [16].
• CPVL is up-regulated during the maturation of monocytes (MO) to macrophages, although the protein can be seen in both [16].
• CPVL has a mixed cytosolic and membrane-associated localization but is not detectable on the outer plasma membrane [16].

Associations of CPVL with chemical compounds

• In primary macrophages, CPVL is glycosylated with high mannose residues and colocalizes with markers for endoplasmic reticulum, while in MO it is more disperse and less clearly associated with endoplasmic reticulum [16].
• CPVL can be seen on early latex bead and Candida albicans phagosomes, but it is not retained in the maturing phagosome, unlike MHC class I/II [16].
• Furthermore, VLP formation by a full-length Gag polyprotein was sensitive to lactacystin, which depletes the levels of free ubiquitin through inhibition of the proteasome [19].
• Removal of heparan sulfate GAGs on keratinocytes by treatment with heparinase or heparitinase resulted in an 80-90% reduction of VLP binding, whereas treatment of cells with laminin, a substrate for alpha6 integrin receptors, provided minimal inhibition [20].
• In contrast to antibody H33.B6, which displays equal efficiencies in pre- and postattachment neutralization assays, H33.J3 does not block VLP binding to heparin, demonstrating that it interferes with steps subsequent to virus binding [21].

Other interactions of CPVL

• Cloning and characterization of CPVL, a novel serine carboxypeptidase, from human macrophages [15].
• Mature pulmonary MØs (alveolar, interstitial, epithelioid and multinucleated giant cells) selectively expressed scavenger receptor type A and a novel carboxypeptidase-like antigen called carboxypeptidase-related vitellogenin-like MØ molecule (CPVL) [1].

Analytical, diagnostic and therapeutic context of CPVL

• Immune responses were measured by an HPV16 L1 VLP-based enzyme-linked immunosorbent assay (ELISA) and by an HPV16 pseudovirion neutralization assay [22].
• METHODS: Volunteers were given intramuscular injections with placebo or with 10- or 50-microg doses of HPV16 L1 VLP vaccine given without adjuvant or with alum or MF59 as adjuvants at 0, 1, and 4 months [22].
• BACKGROUND: Studies in animal models have shown that systemic immunization with a papillomavirus virus-like particle (VLP) vaccine composed of L1, a major structural viral protein, can confer protection against subsequent experimental challenge with the homologous virus [22].
• RESULTS: The presence of HPV16 VLP-specific IgGs in the plasma of the patients was found to be associated with the presence of HPV16 DNA in the cervical smear [3].
• METHODS: Plasma samples from 133 women who had been diagnosed originally with mild to moderate cervical dyskaryosis and enrolled in a prospective non-intervention cohort study conducted in Amsterdam, The Netherlands, from 1991 through 1996 were analyzed for the presence of HPV16 VLP-specific IgGs by use of an enzyme-linked immunosorbent assay [3].

References