The family of T1/35 kDa proteins are secreted, soluble proteins encoded by the '35K' virulence gene of many poxviruses. These proteins have been shown to bind CC-chemokines with high affinity and are now termed viral chemokine inhibitor (vCCI). Viral CCI from various poxviruses share multiple stretches of identical sequence motif and eight conserved cysteine residues. The vaccinia virus (strain Lister) vCCI cDNA encodes a 258 amino acid (aa) residue protein with a putative 17 amino acid residue signal peptide. Vaccinia virus (strain Lister) vCCI shows greater than 90% aa sequence identity with vCCI from other orthopoxviruses and approximately 40% aa sequence identity with the leporipoxvirus T-1 proteins.
Recombinant vCCI has been shown to be a potent general inhibitor of CC-chemokine activity in vitro and blocks binding of CC chemokines to cell surface chemokine receptors. In in vivo studies using a virus mutant in which the gene encoding the CCI has been deleted, leukocyte infiltration into the virus-infected areas is increased, suggesting that CCI can modulate the influx of inflammatory cells into virus-infected tissues.
