Herpes simplex viruses.

Herpes simplex virus (HSV) infections of humans were first The herpes simplex virion consists of four components: (1) an electron-dense core containing viral DNA; (2) an icosadeldocumented in ancient Greece. Greek scholars, particularly Hippocrates, used the word ‘‘herpes,’’ meaning to creep or tahedral capsid; (3) an amorphous, at times eccentric layer of proteins, designated tegument, which surrounds the capsid; crawl, to describe spreading lesions. The classification now in use came into being in the late eighteenth century, and although and (4) an envelope. The capsid consists of 162 capsomeres and is surrounded by the tightly adhering tegument. The envethe vesicular nature of lesions associated with herpetic infections was previously well characterized, it was not until 1893 lope surrounds the capsid-tegument structure and consists of at least 10 glycosylated and several nonglycosylated viral prothat Vidal specifically recognized person-to-person transmission of HSV infections [1]. teins, lipids, and polyamines. Viral DNA contains at least 152 kbp. The variability in size is due chiefly to the variation Following primary infection, neutralizing antibodies to HSV develop in the serum. Subsequently, some seropositive individin the number of reiterations of specific terminal and internal sequences. HSV-1 and HSV-2 DNAs consist of two covalently uals develop clinically mild recurrent labial or genital lesions, typifying the unique biological property of HSV, namely an linked components, designated as L (long) and S (short). Each component is composed of unique sequences (UL or US , reability to recur in the presence of humoral immunity or reactispectively) flanked by relatively large inverted repeats. The vation of latent infection. The spectrum of disease caused by inverted repeat sequences flanking UL are ab and b*a*, whereas HSV includes primary and recurrent infections of mucous those flanking US are a*c* and ca. The two components can membranes (e.g., gingivostomatitis, herpes labialis, and genital invert relative to one another to yield four populations of DNA HSV infections), keratoconjunctivitis, neonatal HSV infection, molecules differing solely in the relative orientation of these visceral HSV infections in immunocompromised hosts, HSV DNA sequences [2]. encephalitis, Kaposi’s varicella-like eruption, and an associaCurrent studies indicate that HSV-1 and, by extension, HSVtion with erythema multiforme. An important advance in our 2 encode at least 84 different polypeptides (figure 1) [3]. Of knowledge of HSV infections has been the ability to distinguish this number, 14 map in the US , four map in each of the sebetween HSV-1 and HSV-2. HSV-1 is more frequently associquences flanking UL , one maps in each of the sequences flankated with nongenital infection, while HSV-2 is associated with ing US , and the remainder map in UL . The genes mapping in genital disease. the repeats are present in two copies per genome. To initiate infection, HSV must attach to cell-surface recepHSV Structure and Replication tors, fuse its envelope to the plasma membrane, and allow the deenveloped capsid to be transported to the nuclear pores. The HSV is a member of a family of viruses whose genomes DNA is released into the nucleus at the core. The key events in consist of a single large double-stranded DNA molecule [1a]. viral replication that occur in the nucleus include transcription, DNA synthesis, capsid assembly, DNA packaging, and envelopment (figure 2). Viral surface glycoproteins mediate attach-