Disease relevance of VP1

• Further analyses showed that U87 was permissive for nuclear transport of MVMi proteins, leading to efficient assembly of empty viral capsids with a normal phosphorylation and VP1-to-VP2 ratio [1].
• We show here that the compact icosahedral parvoviral virion gains entry by deploying a lipolytic enzyme, phospholipase A(2) (PLA(2)), that is expressed at the N terminus of VP1, the minor coat protein [2].
• The VP1- and VP2-specific MAbs have the capacity to neutralize 50% of infectious parvovirus B19 in vitro at 0.08 and 0.73 microgram/ml, respectively, demonstrating the importance of such antibodies in the clearance of B19 viremia [3].
• METHODS AND RESULTS: Myocardial tissue from endomyocardial biopsy, explant, or autopsy was analyzed for parvovirus B19 using primers designed to amplify a 699-base pair PCR product from the VP1 gene region [4].
• We substituted the unique region with a sequence encoding the 147 aa of hen egg white lysozyme (HEL) and constructed recombinant baculoviruses with variable amounts of retained VP1 sequence joined to the VP2 backbone [5].

Psychiatry related information on VP1

• Therefore, the VP1 N-terminal region appears not to be a major determinant of permissiveness for LuIII, versus FPV, capsid in human cells [6].

High impact information on VP1

• A single amino acid substitution in the active site of the VP1 PLA(2) inactivates enzymatic activity and abrogates infectivity [2].
• Immunization of rabbits with capsids composed of VP1 and VP2 resulted in production of antisera that recognized serum parvovirus on immunoblot and neutralized parvovirus infectivity for human erythroid progenitor cells [7].
• Translation of VP1 RNA was very inefficient compared to VP2 RNA in a cell-free system, indicating that capsid protein production was regulated at the level of translation [8].
• However, upon exposure to neutral pH following VP2 cleavage, its VP1-specific sequences and genome are extruded even at room temperature, underscoring the significance of the VP2 cleavage step for MVM particle dynamics [9].
• While incubation of cells with bafilomycin A1 reduced exposure of VP1/VP2 N termini, incubation with chloroquine stimulated externalization transiently [10].

Chemical compound and disease context of VP1

• Testing with a monoclonal antibody recognizing residues 2 to 13 of VP1 (anti-VP1-2-13) and with a rabbit polyclonal serum against the entire VP1 unique region showed that the VP1 unique region was not exposed on purified capsids but that it became exposed after treatment of the capsids with heat (55 to 75 degrees C), or urea (3 to 5 M) [11].
• In convalescence after acute infection, the dominant humoral immune response is directed to the minor capsid protein called VP1, which differs from the major capsid protein by an additional NH2-terminal 227 amino acids [12].

Biological context of VP1

• Each of the deduced amino acid sequences of NS1, NP-1, and VP1/2 showed homology of 96.5%, 92.5%, and 97.5% between the HM-6 and GA3 strains [13].
• Instead, all four BC sequences, which are located in the interior of the capsid, were absolutely required by the incoming infectious MVM particle for the onset of infection, suggesting either an important conformational change or a disassembly of the coat for nuclear entry of a VP1-associated viral genome [14].
• We inactivated the VP1 gene in an infectious clone of MVM DNA by frameshift mutation [15].
• Upon limited heat treatment in vitro, the pores can function as portals to externalize VP1/VP2 protein N-terminal sequences which harbor infection-relevant functional domains, such as a phospholipase A(2) catalytic domain [10].
• The VP1 N terminus contains a number of groups of basic amino acids which resemble classical nuclear localization sequences, including a conserved sequence near the N terminus comprised of four basic amino acids, which in a peptide can act to transport other proteins into the cell nucleus [11].

Anatomical context of VP1

• B19-DNA replication in U937 was accompanied by undetectable level of B19-VP1 mRNA transcription, indicating that B19 infection of U937 cells may be abortive [16].
• The severity of Aleutian disease (AD) was judged by the serum gammaglobulin level, the quantity of peripheral blood CD8 lymphocytes, antibody titers to VP1/2 and NS1 proteins and mink death rates [17].
• Newly synthesized structural polypeptides of parvovirus LuIII, VP1 (62,000 daltons) and VP2 (74,000 daltons), were detected in nuclei of synchronized, infected HeLa cells at 11 to 12 h postinfection, i.e., after cells had passed through the S phase of the cell cycle [18].
• These data indicate that B cells recognizing the VP1/2 capsids receive class II-restricted help from CD4(+) T lymphocytes [19].
• Protein from pCPVEx11, which contains a T cell epitope (peptide PKIFINLAKKKKAG) present in the VP1-specific region as well as the B cell epitopes, seemed to be the most effective in inducing virus neutralization [20].

Associations of VP1 with chemical compounds

• VP2 cleavage and the leucine ring at the base of the fivefold cylinder control pH-dependent externalization of both the VP1 N terminus and the genome of minute virus of mice [9].
• The enzyme activity of the VP1 unique region showed typical Ca(2+) dependency and could be inhibited by manoalide and 4-bromophenacylbromide, which bind covalently to lysine and histidine residues, respectively, as part of the active center of the enzyme [21].
• The presence of drugs modifying endocytosis (amiloride, bafilomycin A(1), brefeldin A, and monensin) caused viral proteins to remain in endosomal/lysosomal vesicles, even though the drugs were not able to inhibit the exposure of VP1 N-terminal end [22].
• CONCLUSIONS: The presence of the glycine-rich sequence in the fivefold channels of MVMi provides a possible mechanism to explain how the unique N-terminal region of VP1 becomes externalized in infectious parvovirions [23].
• However, antibody was not detected in serum from an individual blood donor (Preparation C) in assays performed using kits which contained recombinant VP1 but not VP2 [24].

Other interactions of VP1

• STUDY DESIGN: Heart tissue samples from 110 explants were analysed for PVB19 using primers and a 5'-nuclease probe designed to amplify a 160-basepair PCR product from the VP1/NS1 gene region [25].

Analytical, diagnostic and therapeutic context of VP1

• Antisera raised to this protein recognized recombinant empty capsids containing VP1 and VP2, but not those containing VP2 alone, in an enzyme-linked immunosorbent assay [26].
• Parvovirus capsids were obtained by self-assembly in cell cultures coinfected with either VP1- and VP2-containing baculoviruses or, surprisingly, VP2-containing baculoviruses alone [7].
• Empty B19 capsids composed of VP1 and VP2 could replace serum virus as a source of antigen in a conventional immunoassay for detection of either IgG or IgM antiparvovirus antibodies in human serum [7].
• Specimens with discordant BVP2 EIA and EVP1 EIA results (23 of 24 IgM and 32 of 32 IgG results) were analyzed further by baculovirus-based VP1 immunofluorescence assays (BVP1 IFAs) (Biotrin International) [27].
• Genetic diversity of human parvovirus B19: sequence analysis of the VP1/VP2 gene from multiple isolates [28].

References