SPECIES-SPECIFICITY OF ECTROMELIA VIRUS AND VACCINIA VIRUS INTERFERON-GAMMA BINDING-PROTEINS

Interferon-gamma functions within the immune system as a potent anti-v iral and immunoregulatory cytokine. In order to successfully replicate within a host cell, poxviruses have evolved a number of strategies to counteract the pleiotropic effects of interferon-gamma. In particular , the leporipoxvirus myxoma virus was shown to express an extracellula r soluble interferon-gamma receptor homolog, denoted M-T7, which is ca pable of inhibiting the anti-viral activities of rabbit interferon-gam ma (C. Upton, K. Mossman, and G. McFadden, 1992, Science 258, 1369-137 2). Here, we demonstrate that expression of soluble interferon-gamma r eceptor homologs appears to be characteristic of all poxviruses tested , including Shope fibroma virus, vaccinia virus (strains WR and IHDW), ectromelia virus, cowpox virus, and rabbitpox virus. We have cloned, sequenced, and characterized the interferon-gamma binding protein in s upernatants from ectromelia virus-infected cells, and demonstrate the capability of this soluble protein to bind human, murine, and rabbit i nterferon-gamma with similar affinity. We also investigate the propert ies of the vaccinia virus interferon-gamma binding protein and demonst rate that this protein binds human and rabbit interferon-gamma with si milar affinity and binds murine interferon-gamma with a significantly lower relative affinity. The implications of these studies with respec t to viral pathogenesis and the evolutionary relationship between a vi rus and its host are discussed. (C) 1995 Academic Press, Inc.