Disease relevance of VP3

• The VP3 gene of human group C rotavirus [1].
• It was found that incorporation of the inner capsid proteins into single-shelled particles occurred rapidly, while VP7 and VP3 appeared in mature double-shelled particles with a lag time of 10 to 15 min [2].
• The geometric mean titer of serum neutralizing antibody to a reassortant virus (CJN-M) that contained VP7 of CJN and VP3 of another human rotavirus was 12.7 times less than that of antibody to CJN before infection and 20.3 times less after infection [3].
• The primary translation product predicted on the basis of the plasmid construction was a hybrid protein in which the 98 amino-terminal amino acids of phage MS2 polymerase were followed by amino acids 42 to 387 of the VP3 protein, which included the region containing the cleavage sites associated with trypsin enhancement of infectivity [4].
• Vaccination with double-shelled SA11 virions also elicited cross-reacting antibodies to the outer shell proteins VP3 and/or VP7 which neutralized rotavirus seven times more efficiently than antisera to single-shelled SA11 virus [5].

High impact information on VP3

• Analysis of single (VP3)-gene-substitution reassortants indicated that VP3 was as potent an immunogen as VP7 [6].
• The nucleotide sequence of the VP3 gene of porcine rotavirus OSU [7].
• The inner layer, made of VP2, encloses the genomic RNA and two minor proteins, VP1 and VP3, with which it forms the viral core [8].
• Here, we have characterized the RNA-binding activity of VP3, a minor protein component of the core of rotavirions that has been proposed to function as the viral guanylyltransferase and to direct the capping of the 11 transcripts synthesized from the segmented double-stranded RNA (dsRNA) genome of these viruses [9].
• The N terminus of rotavirus VP2 is necessary for encapsidation of VP1 and VP3 [10].

Biological context of VP3

• Alignment with the porcine group C VP3 equivalent gene showed the human gene is one amino acid longer, and that the proteins have 84.1% amino acid sequence identity [1].
• Analogy with the group A rotaviruses suggested that the genome segment 4 encodes the group C rotavirus guanylyltransferase [1].
• Cleavage of VP3 was not required for virus assembly, and specific cleavage of the polypeptides occurred only on assembled particles [11].
• These data suggest that such a phenotype is not due to alteration of a VP3 function related to transcription [12].
• This indicates that viral morphogenesis is halted after the initial viral transcription and before RNA replication, suggesting that VP3 may be required as part of the replicase system but not for subviral particle assembly [12].

Anatomical context of VP3

• Cell membrane penetration of infectious RRV is initiated by trypsin cleavage of VP3 [13].
• Identification of cytotoxic T cell epitopes on the VP3 and VP6 rotavirus proteins [14].

Associations of VP3 with chemical compounds

• In addition, there is conservation of arginine at the two trypsin cleavage sites as well as conservation of clusters of amino acids in different regions of the two VP3 cleavage products, VP8 and VP5 [15].
• This reassortant derived 10 genes, including gene 4 encoding VP3, from the OSU strain and only gene 9, encoding a major neutralization glycoprotein (VP7), from the Gottfried strain and was thus designated VP3:5; VP7:4 [16].
• UV cross-linking showed that VP3 specifically binds SAM [17].

Regulatory relationships of VP3

• Analysis of single gene 4 substitution reassortants confirmed our previous finding that VP3 was as potent in stimulating neutralizing antibodies as VP7 [18].

Other interactions of VP3

• Characterization of VP1, VP2 and VP3 gene segments of a human rotavirus closely related to porcine strains [19].
• Partial characterization of its remaining VP1, VP2 and VP3 genes along with a porcine rotavirus strain (HP140) uncovered their close genetic relation to porcine strains [19].
• The presence of VP6 with VPdelta2 did not result in encapsidation of VP1 and VP3 [10].
• We propose that the genome segment 3 product be called VP3 and that the gene 4 product be named VP4 from now on [20].

Analytical, diagnostic and therapeutic context of VP3

• Gel shift analysis performed with disrupted (open) virion-derived cores and virus-specific RNA probes showed that VP3 has affinity for single-stranded RNA (ssRNA) but not for dsRNA [9].
• We analyzed cross-reactive neutralization epitopes on protein VP3 of human rotavirus (HRV) by the use of neutralizing monoclonal antibodies (N-MAbs), which showed a variety of interserotypic reactivity patterns when examined in a neutralization test and an enzyme-linked immunosorbent assay against 15 HRV and 2 animal RV strains [21].
• Sequence analysis of the guanylyltransferase (VP3) of group A rotaviruses [22].
• The RNA segment encoding the guanylyltransferase (VP3) from 12 group A rotavirus isolates has been sequenced following RT-PCR and molecular cloning of the full-length amplicons produced [22].
• Guanylyltransferase activity associated with the viral particle was detected by SDS-PAGE due to the formation of a nucleotide-enzyme complex when the virus was incubated with [alpha-32P]GTP [23].

References