Immunology of bovine herpesvirus 1 infection

Abstract

Immune responses to bovine herpesvirus 1 (BHV-1) have been studied following exposure of animals to virulent virus, conventional live or killed vaccines, genetically engineered live virus vaccines, subunit vaccines and, more recently, following immunization with plasmids encoding putative protective antigens. In all cases reported to date, exposure to BHV-1 or its glycoproteins induced specific responses to the virus which are capable of neutralizing virus and killing virus infected cells. These studies clearly indicate that the responses to BHV-1 are broad based, including both Th1 and Th2. In addition to inducing neutralizing antibodies, which can prevent virus attachment and penetration, these antibodies can also participate in antibody complement lysis of infected cells or in antibody dependent cell cytotoxicity. The virus also induces a myriad of specific cellular responses including the induction of cytokines, which either directly or indirectly inhibit virus replication by activation of effector cells. These activities have been associated with lymphocytes, NK-like cells, macrophages and polymorphonuclear neutrophils. These effector cells can kill virus infected cells either directly or by interacting with antibody to induce cell death by antibody dependent cell cytotoxicity. Killing of virus infected cells occurs after the expression of viral antigens on the cell surface of infected cells. Since the relationship between the time of cell killing and completion of virus assembly will influence whether the infectious cycle is aborted or results in productive viral replication any enhancement in viral killing will dramatically reduce the virus load. Based on these studies, many people conclude that antibody is critical in preventing infection and spread to susceptible contacts. In contrast, cell mediated immunity is involved in recovery from infection. However, none of these events occur in isolation in a body and a defect in one will dramatically influence the other. Furthermore, the relative importance of each effector mechanism will clearly depend on whether the animal is exposed to the virus for the first time (primary infection) or it is a secondary exposure following vaccination or infection with the field virus. Following a primary infection, where there is no antibody to interfere with the initial virus-cell interaction at the receptor level, the virus initiates an infection. These initial interactions are mediated primarily by the viral glycoproteins. Following the initial infection, viral protein synthesis induces a series of events which stimulate the nonspecific immune responses of the host. Therefore, the nonspecific immune responses (mediated primarily by viral products which induce early cytokines) are amongst the first line of defense in helping clear the infection both directly as well as indirectly by stimulating the specific immune response. The macrophage is instrumental in focusing the specific immune response by producing various cytokines and subsequently responding to cytokines produced by T-cells to kill to virus infected cells. This activity is detectable within 2 days after infection in lung parenchymal cells and 5–7 days in peripheral blood leukocytes. Interactions between various effector functions in limiting virus replication are described.