Disease relevance of VP7

• Nucleotide sequencing and phylogenetic analysis of 52 Taiwanese G9 rotaviruses showed that the VP7 genes shared a high degree of identity to overseas G9 rotaviruses detected after 1993 and that the VP8* portions of the VP4 genes were more closely related to those of local rotaviruses of other G types [1].
• Self-assembled virus like particles (VLPs) composed by VP2, VP6 and VP7 rotavirus proteins (VLPs 2/6/7) were produced in 5l scale using the insect cells/baculovirus expression system [2].
• Rotavirus assembles in the rough endoplasmic reticulum (RER) and encodes two glycoproteins: VP7, a component of the outer viral capsid, and NCVP5, a nonstructural protein [3].
• The VP4 spike penetrates the virion surface approximately 90 A and interacts with both outer (VP7) and inner (VP6) capsid proteins [4].
• In the presence of the energy inhibitor carbonyl cyanide m-chlorophenylhydrazone (CCCP), processing of VP7 and the vesicular stomatitis virus G protein was blocked at Man8GlcNAc2 [3].

High impact information on VP7

• Our results suggest that assembly of VP4 precedes that of VP7, the major outer shell protein, and that VP4 may play an important role in the receptor recognition and budding process through the rough endoplasmic reticulum during virus maturation [5].
• COS cells transfected with this gene produced VP7 with the correct amino terminus, but the protein was rapidly secreted [6].
• A murine model and "backpack tumor" transplantation were used to determine the protective effect of antibodies against VP4(an outer capsid viral protein) and VP6(a major inner capsid viral protein) [7].
• The present study demonstrates that either in the absence of Ca++ or in the presence of tunicamycin, a glycosylation inhibitor, VP7 is excluded from these hetero-oligomers [8].
• After labeling, glycosylated and nonglycosylated VP7 was recovered in microsomes but the latter was sensitive to trypsin (i.e., the nascent protein became membrane associated) but most of it entered the ER posttranslationally because of a rate-limiting step early in translocation [9].

Chemical compound and disease context of VP7

• Sequence conservation of the major outer capsid glycoprotein of human group C rotaviruses [10].
• An unusual strain of human rotavirus G3P[3] (CMH222), bearing simian-like VP7 and caprine-like VP4 genes, was isolated from a 2-year-old child patient during the epidemiological survey of rotavirus in Chiang Mai, Thailand in 2000-2001 [11].
• Deletions into an NH2-terminal hydrophobic domain result in secretion of rotavirus VP7, a resident endoplasmic reticulum membrane glycoprotein [12].
• Rotavirus VP4-mediated cell entry may involve the alpha2beta1 integrin, whereas VP7 appears to interact with alphaxbeta2 and alpha4beta1 integrins [13].
• In this study, we have examined the requirements for metabolic energy (ATP) for correct folding of the luminal and ER-associated VP7 of rotavirus [14].

Biological context of VP7

• Analysis of the VP7 gene confirmed that these strains belonged to the G3 genotype and shared 97.7% to 98.3% nucleotide identities with other G3 PoRV strains circulating in the regions [15].
• Interestingly, the VP7 sequence revealed highest identity with those of simian G3 rotavirus (RRV strain) at 88% nucleotide and 98.1% amino acid sequence identities [11].
• Furthermore, RFLP analysis of these G1P[8] strains, clearly differentiated the viruses into two main clusters, both of them sharing the same restriction pattern for the VP4 gene, and a different one for the VP7 gene [16].
• Nasuno was also classified into P[12] and G3 in the phylogenetic analysis of the nucleotide sequences of the genome segments encoding VP4 and VP7 [17].
• In recent years it was reported that the accumulation of point mutations in VP4 and VP7 genes of rotavirus strains was the main cause of the failure of the G or P-typing [18].

Anatomical context of VP7

• Primary sequence domains required for the retention of rotavirus VP7 in the endoplasmic reticulum [19].
• However, deletions affecting the second hydrophobic domain (mutants 42-61, 43-61, 47-61) showed immunofluorescent localization of VP7 which coincided with that of wheat germ agglutinin, indicating transport to the Golgi apparatus [12].
• We show that VP4 and VP7 contain tripeptide sequences previously shown to act as recognition sites for integrins in extracellular matrix proteins [13].
• Preincubation of the virus with neutralizing VP7 antibodies inhibited B-cell activation [20].
• In this study, we took advantage of the cytokine flow cytometry technique to obtain a detailed map of H-2b- and H-2d-restricted CD8+ and CD4+ T-cell epitopes from the RV proteins VP6 and VP7 [21].

Associations of VP7 with chemical compounds

• The viral glycoprotein, VP7, is also directed into this compartment and is retained for assembly onto the surface of viral cores [22].
• In pulse-chase experiments in COS cells, nonglycosylated VP7 was still detectable after a 25-min chase period, although the single glycosylation site was only 18 residues beyond the signal peptide cleavage site [9].
• The gene for VP7 potentially encodes a protein of 326 amino acids which has two tandem hydrophobic domains at the NH2-terminal, each preceded by an in-frame ATG codon [12].
• VP7 is therefore a resident ER glycoprotein with a luminal orientation [22].
• VP7 on mature virus was processed to Man5GlcNAc2 [3].

Physical interactions of VP7

• In the presence of Mn++, VP4 was blocked in forming a hetero-oligomeric complex with NS28 and VP7 [8].
• Deletion analysis of VP7 indicated that truncations of either the mature amino or carboxyl terminus disrupted the proper folding of the protein and were not able to coimmunoprecipitate VP6 [23].

Regulatory relationships of VP7

• Interactions between heterologous VP4 and VP7 in reassortants expressing unexpected phenotypes appeared to induce the conformational alterations seen in VP4 [24].
• Analysis of single gene 4 substitution reassortants confirmed our previous finding that VP3 was as potent in stimulating neutralizing antibodies as VP7 [25].

Other interactions of VP7

• VP4 must be added before VP7 for high-level infectivity [26].
• The rotavirus strain was characterized by molecular analysis of its VP4, VP6, VP7, and NSP4 gene segments [11].
• Analysis of single (VP3)-gene-substitution reassortants indicated that VP3 was as potent an immunogen as VP7 [27].

Analytical, diagnostic and therapeutic context of VP7

• Direct reverse transcription-polymerase chain reaction sequencing of VP7 genes from two UK outbreaks (Bristol and Preston) and sequence analysis from a sporadic case of infection from Brazil (Belém) showed that each of these genes was identical in size (1,063 bp) and has revealed a surprising level (97.8-99.8%) of gene sequence conservation [10].
• VP7 was the only gene segment of this strain with significant genetic identity to human strains [28].
• The continuous emergence of VP7-VP4 gene combinations in human rotavirus strains should be taken into consideration when devising vaccination strategies [29].
• G- and P-typing of the positive samples were accomplished by amplifying VP7 and VP4 genes by RT-PCR and genotyped by seminested multiplex PCR methods [30].
• Products from wild-type, and mutants which did not affect the second hydrophobic domain of VP7, were localized by immunofluorescence to elements of the ER only [12].

References