Other vCKBPs

To date, only the mentioned vCKBPs have been studied as potential therapeutic agents. However, a whole set of other vGKBPs from different origins and with different properties and modes of action have been described. Possibly, each of them has evolved to control specific aspects of the activation of the immune response. Therefore, a detailed description of their roles in vivo in their own biological context may help define their potential clinical applications (Table 16.1). Indeed, the examination of the chemokine spectrum bound by each of them in comparison 

CKBP Origin CKs known to bind Mode of action 

35-kDa/M-Tl Poxvirus Broad specificity CC chemokines Block receptor interaction site 

SCPs Poxvirus CCL25, CCL28, CCL27, CCL26, CXCL12, CXCL13, CXCL14 Not determined 

M-T7 Poxvirus Broad specificity CC, CXC, C chemokines Block GAG-binding site 

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I-CCL5 could be detected. The MV M-Tl and SFV ST-1 ORFs show 70% amino acid identity to each other and 40% identity to the W Lister and RPV 35-kDa gene products. Expression of the M-Tl ORF from W WR, which encodes no vCKBP activity, demonstrated that M-Tl encodes the leporipoxvims vCKBP-2. ... 

The discovery of vCKBPs in the poxviruses raised an important question is the production of a secreted vCKBP an immune evasion strategy unique to the poxviruses, or is it also exploited by other mammalian viruses The herpesviruses are an obvious virus family in which to search for novel activities since they, like the poxviruses, have large DNA genomes encoding numerous genes involved in immune evasion. 

The 35-kDa protein or viral CC chemokine inhibitory protein (vCCI) is a secreted protein found in vaccinia virus (VACV) and other poxviruses that binds with high affinity almost all human and mouse CC chemokines [15-17]. The mechanism of action of the 35-kDa protein is competitive inhibition of CC chemokine binding to cellular receptors. The ortholog of myxoma virus (MYXV), named M-Tl, has the unique ability to interact with GAGs via a domain at its C-terminus that is not present in other 35-kDa family members [18]. This unique property of M-Tl would retain the protein in the vicinity of infected cells and may enhance its ability to protect the sites of infection from chemokine-mediated antiviral responses in vivo. Orf virus, a parapoxvirus that causes infections in sheep and cattle, and sporadically in humans, encodes a 35-kDa protein related vCKBP but with a broader chemokine binding specificity that includes the C chemokine lymphotactin [19]. 

Lister) expresses a 35-Kda protein termed 35K, vCKBP (Alcami et al, 1998), or VCCI (Carfi et al, 1999) that binds with high affinity to almost all CC chemokines but does not interact with other classes of chemokines (Smith et al., 1997 Burns et al., 2002). The 35K protein has previously been demonstrated to potently inhibit CC chemokine-induced cell migration and signaling (Bursill et al, 2003). 

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