virF

VirF is a plasmid-encoded transcriptional regulator in Shigella species and related enteroinvasive Escherichia coli. It is a member of the AraC/XylS family of activators and is carried by the virulence plasmid, commonly referred to as pINV. VirF functions as the primary activator of virB, initiating a regulatory cascade that controls the expression of a large set of virulence genes located on the virulence plasmid, including components of the type III secretion system (T3SS) and invasion-associated factors.

In its action, VirF binds to promoter regions on the virB operon and promotes transcription. VirB, in turn, acts as a global regulator that activates a broader regulon, including ipa and other genes essential for invasion of host epithelial cells. Through this cascade, VirF sits at an early entry point in the virulence program of Shigella.

Regulation of VirF is influenced by environmental cues. Expression and activity are favored under host-like conditions, such as body temperature (~37°C), and can be modulated by nucleoid-associated proteins like H-NS, which can repress expression under non-inducing conditions. The regulatory network is tightly controlled to ensure that virulence genes are expressed when invasion is favored.

Structurally, VirF comprises domains characteristic of the AraC family, including regions involved in dimerization and DNA binding, enabling it to regulate target promoters effectively. Functionally, VirF is essential for Shigella pathogenicity; loss of VirF markedly reduces virulence by disrupting the VirF–VirB–downstream gene cascade.

See also: Shigella, pINV, virB, ipa, type III secretion system.