Tumor necrosis factor receptors encoded by poxviruses

Poxviruses encode several cytokine response modifying (Crm) proteins. The Crm proteins possess sequence homology to several human proteins important in immunity. This homology and the conservation of Crm proteins among poxvirus strains suggest an immunomodulatory function that provides a survival advantage to the virus. Cowpox virus encodes several tumor necrosis factor (TNF) receptor family homologues: CrmB, CrmC, and CrmD. CrmB and CrmD encode a similar approximately 155 amino acid COOH-terminus region distal to their TNF ligand-binding portions. These C-terminus regions contain no significant homology with sequences in public databases. It is not known whether the C-terminus regions have a complementary function to the TNF ligand-binding domains, or an unrelated function. Myxoma virus, a rabbit poxvirus, encodes a protein termed T2 which is homologous to CrmB and CrmD. Deletion of the T2 gene results in decreased pathogenicity of myxoma in rabbits. T2 has also been shown to interfere with TNF-induced apoptosis in vitro. Understanding the role viral TNF receptor homologues play in altering host immune responses may suggest ways to develop specific anti-inflammatory therapeutics.