Pathogenesis of Herpes Simplex Virus Infection and Animal Models for Its Study

Abstract

Overcoming infection with herpes simplex virus (HSV) depends upon a complex interaction between virus and host. This interaction most commonly produces asymptomatic infection, as illustrated by the high prevalence of HSV antibodies in individuals with no history of clinically recognized illness (Gibson et al. 1990; Johnson et al. 1989). These findings suggest that host responses are generally effective in limiting viral disease. Clearly this is not always the case since millions of individuals experience symptomatic HSV infections with disease ranging from trivial to life threatening (Whitley 1990). From epidemiological studies and clinical observations we have learned that both viral and host factors may influence whether an individual experiences an asymptomatic infection or is afflicted with severe herpetic disease. Clinical studies, however, are inherently limited and do not permit detailed exploration of the host and viral determinants of disease expression. The use of well-characterized experimental animal models has proven invaluable in further defining the natural history of HSV infection. With the recent advances in molecular biology and immunology, animal models are being increasingly used to investigate the role of selected viral genes and specific immune responses in the pathogenesis and immunobiology of HSV infection. This chapter will review the experimental animal models used to study HSV and summarize our current understanding of the pathogenesis of infection, with a primary focus on genital herpes. The immunobiology of HSV, as it pertains to viral pathogenesis and animal model research, will receive minimal attention in this chapter but will be presented in greater detail in other chapters in this volume.