Introduction

In this chapter the emphasis is on viral replication and on the viral gene products that define the outcome of the interaction of the alphaherpesviruses with their host. Viral replicative and host management functions account for some of the RNAs and a large number of proteins encoded by the viruses. There are, however, numerous viral gene products whose functions have not been identified or which do not play a prominent role in viral replication in the systems in which these have been tested. The objective of the table contained in this section is to summarize the functions of all known gene products and provide at least a few references for each product. It should be noted however that: of the three human alphaherpesviruses, we know more about the functions of herpes simplex virus-1 and -2 (HSV-1 and HSV -2) genes than about those of varicella zoster virus (VZV). We have identified in this table the VZV genes that are related to HSV by amino acid sequence homology. We note that partial sequence conservation does not necessarily mean that the homologous HSV and VZV gene products perform identical functions.

The list understates both the number of the products and their functions. The problem is twofold. The HSV genome encodes a large number of open reading frames (ORFs) with 50 or more codons and not all of the ORFs have been probed for to determine whether they are expressed.

Diseases caused by the human herpesviruses were recognized by the earliest practitioners of medicine. Hippocrates, Celsus, Herodotus, Galen, Avicenna and others described cutaneous lesions typical of infections caused by herpes simplex viruses (HSV) 1 and 2, and varicella-zoster virus (VZV). ‘Herpes,’ the family name of these viruses, is traced to the Greek term for lesions that appeared to creep or crawl over the skin. Among the duties of John Astruc, physician to King Louis XIV, was to understand the diseases of French prostitutes, in Latin, the ‘Puellae publicae’, which led to his description of herpes genitalis. Distinguishing between genital herpes and syphilis was an obvious concern in this social context as it is now. The modern scientific investigation of HSV can be dated to the work of Gruter, who first isolated the virus and demonstrated its serial transmission in rabbits. During the 19th century, experiments in human subjects showed that HSV and VZV could be transmitted from fluid recovered from HSV and VZV lesions. Demonstrating that Koch's posulates were fulfilled was important but arguably the truly revolutionary discovery about the herpesviruses was made by Andrews and Carmichael in the 1930s who showed that recurrent herpes labialis occurred only in adults who already had neutralizing antibodies against HSV.

Introduction

The fundamental mission of all viruses is to replicate and spread, and above all, to persist in the host environment to which they have become adapted. Viruses vary with respect to the mechanisms by which they attain their objectives. This variation is reflected not only in the basic mechanisms of viral entry into cells, synthesis of viral proteins, viral nuclei acid synthesis, virion assembly, and egress but also with respect to the basic strategies by which they preclude the enormous resources of the host cell and of the multicellular organism from totally blocking viral replication. The terminology used: “totally blocking” is appropriate; in essence the evolution of functions encoded in the viral genome reflects a fundamental accommodation between replication and spread as well as persistence in the human population. A replication and spread that kills the host will not permit the survival of the virus. The objective of this chapter is to examine the basic strategies evolved by HSV to replicate in its cellular environment.

Gene content, organization, and fundamental design of the viral genome

Several aspects of the structure, content and function of the viral genome are worthy of note. They are as follows.

(i) We do not know with any degree of certainty the exact number of transcriptional units or proteins encoded by the viral genome. The problem stems from several considerations. […]