INTERRUPTION OF CYTOKINE NETWORKS BY POXVIRUSES - LESSONS FROM MYXOMAVIRUS

Myxoma virus is an infectious poxvirus pathogen that induces a virulen t systemic disease called myxomatosis in European rabbits, The disease is rapidly and uniformly fatal to susceptible rabbits and is characte rized by generalized dysfunction of cellular immunity and multiple int erruptions of the host cytokine network, A number of virus genes are c lassified as virulence factors because virus constructs bearing target ed gene disruptions induce attenuated disease symptoms, Many of these genes encode proteins that interact directly with effector elements of the host immune system. Included among these immunosubversive viral p roteins are secreted mimics of host ligands or regulators (virokines) and homologues of cellular cytokine receptors (viroceptors). Five exam ples of these immune modulator proteins encoded by myxoma virus are re viewed: (1) myxoma growth factor, a member of the epidermal growth fac tor ligand superfamily; (2) SERF-1, a secreted serine proteinase inhib itor; (3) M11L, a receptor-like surface protein; (4) T2, a tumor necro sis factor receptor homologue; and (5) T7, an interferon-gamma recepto r homologue, The origin of viral strategies designed to subvert immune regulation by host cytokines is considered in the context of the biol ogy of myxoma virus within immunocompetent hosts.