Using the preimmune sera from inbred and outbred pigs, no plaque reduction was found. number of herpesviruses, the design of future antiherpesvirus vaccines should aim to induce a humoral immune response that prevents HBD-mediated viral attachment. Herpesviruses persist in the natural host for the life of the host, and therefore, they must be able to evade the host’s immune mechanisms directed against the virus and virus-infected cells. Besides establishing a latent infection and thereby escaping direct immune attack, herpesviruses employ a variety of strategies to directly interfere with the Mouse monoclonal to CHUK immune system, e.g., expression of functional homologues or receptors of cytokines, chemokines, and the major histocompatibility complex (MHC) class I molecules (5). Such sophisticated evasion strategies FR183998 free base can explain why vaccination against herpesviruses has only limited success. Although vaccines can prevent symptoms of the disease, they do not eliminate the virus from the infected host and do not prevent the establishment of a latent infection. Pseudorabies virus(PRV), a member of theAlphaherpesvirinae, is the causative agent of Aujeszky’s disease. In pigs, the natural host of PRV, mortality decreases with increasing age, and upon primary infection a latent infection that can be reactivated is generally established (45). Since outbreaks of Aujeszky’s disease cause important economic losses, attenuated live viruses or inactivated vaccines FR183998 free base are widely used for vaccination of pigs. Glycoprotein gC of PRV plays an important role in eliciting a protective immune response in pigs. Vaccinations with protein fractions enriched for PRV gC, recombinant gC subunit vaccine, and gC vaccinia virus recombinants as well as vaccination with DNA encoding gC were found to provide protection against PRV challenge (11,16,32). Several immune mechanisms directed against gC have been reported to combat PRV infection. PRV infection can induce MHC class I restricted, gC-specific, cytotoxic T cells (52). It was also shown that gC is involved in priming of porcine T-helper cells (17) and induces MHC class II restricted, PRV-specific memory T-helper cells (30). In addition to its role in the specific cell-mediated immune response, gC also is one of the major viral proteins that trigger the porcine humoral immune response. In pigs, the majority of virus-neutralizing antibodies induced by PRV infection or vaccination with attenuated live virus is directed against gC (1). Passive immunization of pigs with gC-specific mouse monoclonal antibodies was sufficient to confer protection (24), indicating that gC-specific antibodies, even in the absence of a cell-mediated immune response, play an essential role in the control of PRV infection. PRV gC, which is a constituent of the viral envelope (34,35), is nonessential for virus growth in tissue culture (34,44) but is required for maximum infectivity, as mutant virions lacking gC have been shown to be defective in attachment to target cells (25). The attachment defect of gC-negative virions is due to a failure to bind to heparan sulfate glycosaminoglycan chains on the target cell (28). It was further shown that the heparan-binding protein gC is promoting the initial attachment of the virus (13) and that three functional heparin-binding domains (HBDs), located in the amino-terminal part of gC (Fig.1), mediate this interaction (7,8,21). The single domains are each composed of a cluster of positively charged viral amino acids with homology to the HBD consensus sequence (2). Each separate HBD is able to promote attachment to target cells (8). == FIG. 1. == Schematic representation of the FR183998 free base gC protein. The location of the three fusion proteins gC-N-term, gC-middle, and gC-C-term is indicated by the.