Controlling herpes simplex virus infections: is intracellular immunization the way of the future?

Abstract

The available approaches to the management of herpes simplex virus (HSV) infections currently consist primarily of chemotherapy and the possibility of preventive vaccination. In this review, we explore the potential of a third approach based on recent advances in molecular biology and genetic engineering which renders cells resistant to viral infection. This form of antiviral gene therapy, termed “intracellular immunization” by Baltimore (1988), involves the intracellular expression of a variety of molecular species specifically designed to inhibit targeted virus replication. The utility of such an approach lies in the direct application of knowledge pertaining to molecular mechanisms involved in viral pathogenesis to precisely interrupt lytic infection through the generation of virus-resistant cells. Such strategies may be particularly useful in the management of intracel-lular pathogens which are capable of evading the immune system or in circumstances in which knowledge of molecular pathogenic mechanisms far surpasses the ability to develop appropriate therapeutic drugs or vaccines. In this article, the basic concepts of intracellular immunization, relevant aspects of HSV molecular biology, and studies utilizing antiviral gene therapy to prevent HSV infection will be reviewed.KeywordsHuman Immunodeficiency VirusHuman Immunodeficiency Virus TypeHerpes Simplex Virus TypeRibonucleotide ReductaseHerpes Simplex Virus InfectionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.