to NF-kappa-B essential modulator (NEMO) and has not been identified in other poxviruses (Figure 3).13 Interestingly, the molecular structure of MC005 differs slightly in MCV-1 and MCV- 2. In MCV-1, it is 89-amino-acids (9-kDa), whereas, it is shorter in MCV-2. It is believed this characteristic may differentiate MCV-1 and MCV-2 in infected populations.13
A novel mechanism for MCV to inhibit human innate immunity and potentially contribute to persistent MC lesions is the effect of MC132 on the NF-κB pathway. NF-κB is inhibited by the MC132 protein which recruits Cullin-5/Elongin B/Elongin C complex, and binds directly to P65, an NF-κB subunit, thus inducing ubiquitination and subsequent degradation of P65 (Figure 3).26
MC159 and MC160 prevent the degradation of IκBβ, albeit by a distinct mechanism of action (Figure 3). It is suggested that MC159 inhibits degradation of IκBβ whereas MC160 inhibits degradation of IκBβ, a stronger inhibitor of NF-κB than IκBβ.27 MC160 inhibits the acute NF-κB pathway during the early stage of infection and MC159 inhibits chronic effects of NF-κB during the chronic infection.28–30 MC159 also inhibits CD-95 and TNF induced apoptosis via binding to the Fas-associated death domain (FADD) (Figure 4).8,31 Lastly, MC159 and MC160 have been shown to inhibit interferon regulatory factor (IRF) 3 via direct and indirect inhibition, respectively. IRF3 is an essential transcription factor for the production of interferon (IFN) β, a molecule with potent antiviral effects by inhibiting viral multiplication.32 Decreased levels of IFN-β contribute to the low immune response in MC. A recent study showed that inserting MC159 and MC160 genes into VV increased infectivity of the
