virus.11,33 This implicates MC159 and MC160 have potential for applications in medicine and research.
MC163 is another protein that aids in inhibition of the complex NF-κB pathway by inhibiting TNF-α from activating NF-κB, as well as dampening inhibitory-κB kinase (IKK) α and β activation of NF-κB.34,35 However, MC163 also has a unique mechanism of inhibition of apoptosis. During regular apoptosis, mitochondria normally have increased permeability to cytochrome c that helps in signaling controlled cell death. MC163 binds to the mitochondrial membrane and decreases the permeability of cytochrome c, thus inhibiting apoptosis (Figure 5).36
Alternate MC Protein Pathways
Besides NF-κB pathway, MC proteins also act on other molecules within the realm of immune activation. Interleukin -18 (IL-18), a potent inducer of T-helper 1 (Th-1) response and Interferon-γ (IFN-γ), is imperative in defending against viral invasion. IL-18 is also known as IFN-γ inducing factor and may be responsible for conditions that involve autoimmunity. Studies have demonstrated that the IL-18 binding protein (IL-18- bp) suppresses the overactive immune system and protects the host.37 Studies have also shown that MC53 and MC54 in MCV bind to IL-18 and function as an IL-18-bp to neutralize the IL-18.38,39
Along with herpesviruses, poxviruses are the only viruses to code for human chemokine and chemokine-binding protein homologs.10 One such protein encoded by MC, MC148, posits as an inhibitor for chemotaxis of immune cells. The exact mechanism is still elusive. Two models were proposed. One suggests that MC148 binds to chemokines and prevents them from reaching their receptor. The other model suggests that MC148 binds to chemokine receptors directly. MC148 competes with macrophage inflammatory protein (MIP)-1 binding to chemokine receptors 2B and 8 (CCR2B and CCR8).10 CCR2B is an adhesion molecule utilized by various viral infections, including
