African Swine Fever Virus IAP-Like Protein Induces the Activation of Nuclear Factor Kappa B

To be, or not to be: NF-κB is the answer – role of Rel/NF-κB in the regulation of apoptosis

“…The early viral protein A238L acts like a degradationresistant mutant of IkB to blunt the initial burst of NF-kB activity that follows infection and suppress host immune and inflammatory responses. On the other hand, the IAP-like ASFV protein A224L is expressed later during the course of infection and activates NF-kB via the IKK kinase complex to seemingly suppress apoptotic caspases and lengthen the infection (Rodriguez et al, 2002).…”

Manipulation of the nuclear factor-κB pathway and the innate immune response by viruses

“…The ASFV IAP-like protein A224L can activate IKK and consequently NF-kB when stably expressed in Jurkat T cells (Rodriguez et al, 2002). A224L is expressed late in infection and may prevent apoptosis (and thus prolong the viral infection state) both by blocking caspase activity and by inducing NF-kB activity.…”

Exacerbated inflammatory responses in transgenic mice expressing an inhibitor of apoptosis protein (OpIAP)

“…A recent report showed that cultured T cells expressing the African swine fever virus IAP homologue induced NF-kB activation, which was associated to elevated IKK activity. 9 Further studies are required to determine the exact mechanism by which OpIAP induces NF-kB translocation to the nucleus.…”

“…Some IAPs induce activation of the transcription factor NF-kB by increasing its nuclear levels. [6][7][8][9][10] The baculoviral OpIAP was one of the first IAP family members identified; it shares the characteristic structural composition with cellular counterparts such as XIAP, c-IAP1 and c-IAP2: two BIR motifs located in the amino-terminal region and a RING zinc finger in the carboxy-terminus of the protein. 2 Although OpIAP was originally described as a caspase inhibitor in insect cells, 11 it also inhibits apoptosis when expressed in mammalian cells.…”

“…13 Previous work showed that the expression of some IAPs is associated with increased nuclear levels of NF-kB via an unknown pathway. [7][8][9] Since NF-kB is an essential regulator of the T-cell response, we used T-lineage-specific tg expression in mice to study the effects of the IAP protein OpIAP on Tlymphocyte function and physiology. The data illustrate a new role for IAPs in T-cell responses; OpIAP enhances Tlymphocyte activation, proliferation and cytokine production probably by increasing nuclear NF-kB levels.…”