Disease relevance of PT40

• The sequence shows extensive homology with other parvoviruses such as MVM, H-1, CPV, and FPV in the capsid coding region [1].
• Nucleotide sequence analysis of the capsid genes and the right-hand terminal palindrome of porcine parvovirus, strain NADL-2 [1].
• Influenza and adenoviruses undergo extensive disassembly prior to genome import; herpesviruses release their genome into the nucleus without immediate capsid disassembly [2].
• In normal individuals, examination of paired sera showed that the dominant humoral immune response during early convalescence was to the virus major capsid protein (58 kD) and during late convalescence to the minor capsid species (83 kD) [3].
• Empty capsid production was equal to or greater than virion production by infected bone-marrow cells, 1000-2000 capsids per cell, but cell growth was not diminished by capsid production [4].

High impact information on PT40

• Viral DNA and capsid protein were present in the bone marrow of three patients studied, and active viral replication was detected by southern analysis [5].
• Significantly, highly efficient rescue can be achieved by polyethyleneimine-induced endosome rupture or by coinfection with adenovirus as long as uptake of the two viruses is simultaneous and the adenovirus is capable of deploying pVI, a capsid protein with endosomolytic activity [6].
• Twenty-eight amino acid residues involved in most noncovalent interactions between trimeric protein subunits in the capsid of the parvovirus minute virus of mice were truncated individually to alanine, and the effects on capsid assembly, thermostability, and conformation were analyzed [7].
• A cell line, designated 3-11-5, stably expressed nearly full-length transcripts for the two capsid proteins [4].
• Capsid protein was present in both nuclei and cytoplasm on immunofluorescence study but fractionated with the cytosol on purification [4].

Chemical compound and disease context of PT40

• Host-selected amino acid changes at the sialic acid binding pocket of the parvovirus capsid modulate cell binding affinity and determine virulence [8].
• Using recombinant viruses transducing a luciferase reporter, we show that insertion of a cyclically constrained, integrin-binding peptide at an exposed position on the FPV capsid enables transduction of an alpha(v) integrin-expressing human rhabdomyosarcoma cell line (Rh18A) [9].
• The capsid proteins of the ADV-G isolate of Aleutian mink disease parvovirus (ADV) were expressed in 10 nonoverlapping segments as fusions with maltose-binding protein in pMAL-C2 (pVP1, pVP2a through pVP2i) [10].
• Virions of minute virus of mice were purified by sedimentation in sucrose gradients and chromatography on DEAE-cellulose columns and shown to consist of single-stranded viral DNA and the viral capsid polypeptides VP-1 (83 kDa) and VP-2 (64.5 kDa) [11].
• Effect of a valine residue at codon 352 of the VP2 capsid protein on in vivo replication and pathogenesis of Aleutian disease parvovirus in mink [12].

Biological context of PT40

• The genome of the porcine parvovirus, strain NADL-2, has been cloned and the sequence of map units 28 to 100, which is 3670 bp in length and contains the capsid coding regions and the right-hand terminal palindrome, has been determined [1].
• Given the information available from these sequences, the regulatory and capsid coding regions for PPV have been proposed and the amino acid sequences of capsid proteins compared [1].
• Irreversible capsid dissociation as detected by changes in fluorescence, hemagglutination activity, and electrophoretic mobility occurred at much higher temperatures [13].
• By cotransfecting with a helper plasmid expressing the capsid proteins, it was possible to produce mixed virus stocks containing MVM/P38cat infectious particles and variable amounts of recombinant MVM [14].
• The observed differences in loop topologies at subunit interfaces are consistent with the inability of AAV2 and AAV4 VPs to combine for mosaic capsid formation in efforts to engineer novel tropisms [15].

Anatomical context of PT40

• Two murine parvoviruses with genomic sequences differing only in 33 nucleotides (8 amino acids) in the region coding for the capsid proteins show different host cell specificities: MVMi grows in EL4 T lymphocytes and MVMp3 grows in A9 fibroblasts [16].
• These results indicate that MVM maturation proceeds by cytoplasmic oligomerization of the capsid subunits into two types of trimers, which are the assembly intermediates competent to translocate across the nuclear membrane [17].
• We produced overlapping fusion proteins to span the viral capsid sequence, inoculated rabbits, and determined whether the resulting antisera contained antibodies that neutralized the ability of the virus to infect human erythroid progenitor cells [18].
• Inside lysosomes, capsid degradation was not detected, although the uncoated DNA of FC was slowly degraded [19].
• Microinjection of several capsid-specific antibodies into the cell nucleus blocked AAV2 infection completely, supporting the conclusion that AAV2 capsids bring the infectious genome into the nucleus [20].

Associations of PT40 with chemical compounds

• When four or more methylene-sized groups were introduced, or six or more groups removed, capsid assembly was drastically impaired [21].
• The capsid proteins of the full virus, on the other hand, were completely unreactive to dimethylsuberimidate [22].
• Expansion of tropism of a feline parvovirus to target a human tumor cell line by display of an alpha(v) integrin binding peptide on the capsid [9].
• Mutations in any or all four serine residues present in peptide B showed that the VP-2 N-terminal domain is phosphorylated at multiple sites, even though none of them was essential for capsid assembly or virus formation [23].
• Lysine 531 is unique to AAV6 among other known AAV serotypes and is located in a basic cluster near the spikes that surround the icosahedral threefold axes of the AAV capsid [24].

Analytical, diagnostic and therapeutic context of PT40

• Appropriate ratios of major and minor capsid proteins were determined by immunoblot, and newly synthesized capsid protein was detected by immunoprecipitation of radioactively labeled cell lysates [25].
• Antibodies that bound to virus in an enzyme-linked immunosorbent assay were present in antisera raised against 10 of 11 peptides; strongest activity was found for antisera against the carboxyl-terminal half of the major capsid protein [18].
• We investigated the role of the NH2-terminal region of the major structural protein in capsid structure by expressing progressively more truncated versions of the VP2 gene followed by analysis using immunoblotting and electron microscopy of density gradient-purified particles [26].
• The new structures, determined by X-ray crystallography to 3.2 and 3.3 A resolutions, respectively, clearly showed differences in the interactions of residue 93 with an adjacent loop on the capsid surface [27].
• The three-dimensional structures of the viral capsid of three AAV serotypes have previously been determined by X-ray crystallography or cryoelectron microscopy [28].

References