Large DNA viruses defend against hostile assault executed by the host immune system by producing an array of gene products that systematically sabotage key components of the inflammatory response. Poxviruses target many of the primary mediators of innate immunity including interferons, tumor necrosis factors, interleukins, complement, and chemokines. Poxviruses also manipulate a variety of intracellular signal transduction pathways such as the apoptotic response. Many of the poxvirus genes that disrupt these pathways have been hijacked directly from the host immune system, while others have demonstrated no clear resemblance to any known host genes. Nonetheless, the immunological targets and the diversity of strategies used by poxviruses to disrupt these host pathways have provided important insights into diverse aspects of immunology, virology, and inflammation. Furthermore, because of their anti-inflammatory nature, many of these poxvirus proteins hold promise as potential therapeutic agents for acute or chronic inflammatory conditions.

Our results suggest that signaling from the focus induces nested rings of regulatory gene expression that subsequently control the final color pattern. Furthermore, the remarkably plastic regulatory interactions downstream of focal signaling have facilitated the evolution of eyespot diversity.

In patients suffering from recurrent facial or genital herpes simplex virus (HSV) infection or from shingles caused by varicella-zoster virus (VZV) infection in the skin, virus reactivation from latently infected sensory neurons is followed by rapid spread of infection through epidermal tissues. These alphaherpesviruses are extremely adept at moving from infected to uninfected epithelial cells and between neurons and other cells in the nervous system. Rapid and efficient progression of virus infection through tissues is particularly important, especially immediately following reactivation, when alphaherpesviruses race to produce progeny and spread to other hosts in the face of robust and fully primed host immunity. Cell-to-cell spread in epithelial tissues involves movement of virus particles across cell junctions, in a space that is resistant to the effects of virus-neutralizing antibodies. This process probably explains, in part, observations that the levels of neutralizing antibodies do not predict the severity of HSV lesions or the time to recrudescence (11).HSV, VZV, and pseudorabies virus (PRV) express a heterodimer of two membrane glycoproteins, gE and gI, that functions to mediate cell-to-cell spread in epithelial and neuronal tissues (4, 9, 10, 12, 14, 18-20, 23-25, 28, 32, 33, 40, 42, 45). HSV and PRV gE/gI complexes are required for efficient spread of viruses between certain cultured epithelial cells, neurons, and other polarized cells with extensive cell junctions but are not needed for spread between highly transformed, nonpolarized cells, which do not form cell junctions (12,13,27,42,47,51). For example, plaques formed by a gE-negative HSV mutant on monolayers of a keratinocyte cell line included eightfold fewer cells than plaques produced by wild-type HSV-1, yet there was no difference in cell-to-cell spread in monolayers of HeLa cells (47). Moreover, PRV and HSV gE/gI complexes are required for spread within synaptically connected neuronal circuitry in the peripheral and central nervous systems (3,13,32,40,42,45). gE and gI are extensively complexed in virus-infected cells (19,20), and it is the gE/gI complex that functions in cell-to-cell spread (12,13,19,20,35,42,52). In contrast to their effects on cell-to-cell spread, HSV and PRV gE/gI complexes do not appear to be required for entry of cell-free virus, i.e., virus particles applied to the apical surfaces of cells (12,27). Given this observation and the specialized effects of gE/gI in polarized cells or cells that form extensive cell junctions, we hypothesized that gE/gI functions specifically in the movement of virus to and across cell junctions (14, 47). Consistent with this hypothesis, gE/gI can accumulate extensively at cell junctions after infection with HSV (14, 26a, 47).The cytoplasmic domains of HSV and PRV gE/gI are essential for the process of cell-to-cell spread (26a, 39, 42, 47). These cytoplasmic domains, and those of VZV gE/gI, contain tyrosine (YXXØ, where Ø is a bulky hydrophobic amino acid)