The host response to herpes simplex virus infection

Infection with herpes simplex virus remains a significant cause of disease. The host immune system plays an important role in containing viral replication, and there has been considerable progress in defining which components of immunity are key to the resolution of infection. Nevertheless, effective immunoprophylaxis or immunotherapy has not yet been achieved.

Recent work has focused on understanding the early events leading to the herpes simplex virus-specific immune response, in particular on the role of antigen-presenting dendritic cells. Herpes simplex virus has evolved a number of ways of interfering with antigen presentation by dendritic cells, thus presumably impeding or delaying the host immune response. Nevertheless, herpes simplex virus triggers strong cellular and humoral immunity. The ability of dendritic cells to take up dead or dying infected cells and cross-present them to cognate T cells may be the key to resolving this apparent paradox. Interaction between dendritic cell subsets, and particularly the virus-induced release of type I interferons may be essential to drive efficient antigen cross-presentation and subsequent T-cell activation.

A greater understanding of the importance of dendritic cells in driving viral immunity, and of the ligands that activate these cells and the cytokines they secrete, has provided novel vaccination strategies. The delivery of immunomodulatory genes together with viral antigens, for example by DNA vaccination, may harness the full potential of dendritic cells, and achieve the goal of effective immunological control of herpes simplex virus.