TNF-Binding Proteins Unrelated to Host TNFRs

Viral TNF-Binding Proteins Unrelated to Host TNFRs 

Viral Proteins Hiat Modulate TNF Receptors and Regulate Downstream Signaling 

Poliovirus noncapsid protein 3A is a multifunctional viral protein involved in poliovirus RNA replication. One of its functions is suppression of protein trafficking between the ER and Golgi apparatus. In infected cells, it affects the intracellular trafficking of TNFR and induces TNF resistance by eliminating TNFRs from the plasma membrane. This 3A-protein-mediated inhibition of ER to Golgi traffic ofTNFR was limited to poliovirus and coxsackievirus B3. Further investigation is required to understand whether this inhibition is selective for TNFR or not. 

Cell Simaling Inhibitors from Viruses Ihat Inhibit Activation ofNF-KB 

The ideal candidate for a virus-derived anti-TNF therapeutic would be more specific and less toxic to the human system than current therapies. Several viral inhibitors can specifically block intracellular s naling, often resulting in reduced TNF production or its TNFR-dependant effects. Activation of NF-kB is an early event that occurs within minutes after exposure to TNF and plays important role in inflammation, regulation of cell proliferation, activation and survival. This activation process has turned out to be an attractive target for viruses to escape immune defenses and many viruses have evolved specific gene products to inhibit the TNF-induced NF-kB activation. 

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