Disease relevance of virG

• The ability of Shigella to spread within and between epithelial cells is a prerequisite for causing bacillary dysentery and requires the function encoded by the virG gene on the large plasmid [1].
• A novel virulence gene (virA) was identified upstream of the virG gene on the large plasmid of Shigella flexneri 2a YSH6000 [2].
• Further characterization of delta aroA delta virG Shigella flexneri 2a strain CVD 1203 as a mucosal Shigella vaccine and as a live-vector vaccine for delivering antigens of enterotoxigenic Escherichia coli [3].
• EcSf2a-3 was derived from EcSf2a-2 by introducing a deletion in the virG gene, whose expression is required for plaque formation and keratoconjunctivitis in guinea pigs [4].
• To express human papillomavirus (HPV) L1 capsid protein in the recombinant strain of Shigella and study the potential of a live attenuated Shigella-based HPV prophylactic vaccine in preventing HPV infection, the icsA/virG fragment of Shigella-based prokaryotic expression plasmid pHS3199 was constructed [5].

High impact information on virG

• We have identified a region (virG) on the 230 kb virulence plasmid of S. flexneri that is required for cell-to-cell spread of the bacterium [6].
• The virG region was localized to within 4 kb and may contain a single cistron [6].
• Identification of icsA, a plasmid locus of Shigella flexneri that governs bacterial intra- and intercellular spread through interaction with F-actin [7].
• The nucleotide sequence of the virA region revealed that the virA gene was located 528 bp upstream of the virG gene, in the opposite orientation [2].
• In contrast, the activation of the virG gene necessary for intercellular spread occurred directly by virF without the requirement for virB [8].

Chemical compound and disease context of virG

• The Shigella flexneri 2a SC602 vaccine candidate carries deletions of the plasmid-borne virulence gene icsA (mediating intra- and intercellular spread) and the chromosomal locus iuc (encoding aerobactin) (S. Barzu, A. Fontaine, P. J. Sansonetti, and A. Phalipon, Infect. Immun. 64:1190-1196, 1996) [9].

Biological context of virG

• The observed phenotype of M94 in the cytoplasm indicated that the virG locus is not required for multiplication of the invading shigellae, but is essential for their spread to adjacent cells [10].
• Characterization of the vacC mutant indicated that levels of VirG, a protein essential for bacterial spreading, and VirF, the positive regulator for the expression of the virG and ipaBCD operons, decreased significantly compared with those of the wild type [11].
• The nucleotide sequence of 4,472 bp, which contains the functional virG gene and its own regulatory sequence, was determined, and a large open reading frame encoding 1,102 amino acid residues was identified [10].
• Results obtained from molecular genetic studies, mainly of the genes, virG, virF and kcpA are discussed [12].

Anatomical context of virG

• A stable strain, S. sonnei Mosely, was selected for further work. pDeltavirG2, a deletion derivative of the virG gene in the sacB suicide vector pCVD442, was used to generate an S. sonnei virG deletion strain, WRSS1, which was invasive in HeLa cells but negative in the Sereny test [13].
• This vaccine strain was constructed by deletion of virulence genes responsible for dissemination (icsA) and survival (iuc:iut) of bacteria within the colonic mucosa [14].

Other interactions of virG

• virF is the master regulator which activates the virulence determinant genes of Shigella spp. such as ipaBCD and virG [15].

References