Functional consequences of HSV-1 infection of dendritic cells

• Main Author: Pollara, Gabriele
• Published: University College London (University of London) 2005
• Subjects: 616.522
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416594

Herpes simplex virus-1 (HSV-1) infects a significant proportion of the population, causing widespread morbidity and occasional mortality. An understanding of the interaction of this virus with the immune system will aid in the development of vaccines to reduce the prevalence of this infection, and in evaluating its potential role as a vector in immunotherapy. Dendritic cells (DC) are the critical initiators of adaptive immune responses to HSV-1 and are likely to encounter the virus early after infection of the skin or mucosa. This thesis aims to describe the functional consequences of the interaction between HSV-1 and DC. DCs are readily infected by HSV-1. The function of these cells is affected in a multitude of ways. The capacity of infected DC to stimulate T cell proliferation is reduced, following changes in morphology, IL-12 secretion and surface phenotype. However, the infection of DC by HSV-1 also results in activation of both infected and uninfected cells. The secretion and paracrine activity of type IIFN is responsible for the activation of bystander DC and plays an important amplifying role in the secretion of IL-12 by these cells. In contrast, HSV-1 envelope structures bind to the surface of DC and induce maturation directly. The binding of HSV-1 glycoprotein D is critical to the acquisition of this mature phenotype. In the context of natural HSV-1 infection, these findings suggest the hypothesis that the coupling of viral entry to the activation of DC signalling pathways is counterbalanced by viral disruption of DC maturation. This delays the generation of the immune responses to HSV-1. Nonetheless, the parallel release of type I IFN, resulting in paracrine activation, enables other DC to mount an antiviral immune response.