Elsevier

The Lancet

Volume 357, Issue 9267, 12 May 2001, Pages 1513-1518
The Lancet

Review
Herpes simplex virus infections

https://doi.org/10.1016/S0140-6736(00)04638-9Get rights and content

Summary

Herpes simplex virus (HSV) is a member of the herpesviridae family. Recognised since ancient Greek times, the virus frequently infects human beings, causing a range of diseases from mild uncomplicated mucocutaneous infection to those that are life threatening. In the past 50 years, substantial advances in our knowledge of the molecular biology of HSV have led to insights into disease pathogenesis and management. This review provides a contemporary interpretation of the biological properties, function, epidemiology, and treatment of HSV diseases.

Section snippets

Structure

HSV-1 and HSV-2 contain a large double-stranded DNA molecule.1 The HSV virion has four parts: an electrondense core containing viral DNA; an icosapentahedral capsid; a tegument—an amorphous layer of proteins that surround the capsid; and an envelope. The DNA of HSV-1 and HSV-2 consists of two covalently linked components, L (long) and S (short), with unique sequences—UL (unique long) or US (unique short)—flanked by large inverted repeats. The two components can invert relative to one another,

Viral function

Several parts of the viral replication cycle and the resulting proteins are relevant to the study of human disease and antiviral therapy. For example, viral surface glycoproteins mediate attachment and penetration of HSV into cells, and provoke host immune responses. There are 11 known viral glycoproteins (B–M) and a 12th (gN) is predicted. Two of these glycoproteins (gB or gD, or both) have been used in subunit vaccines. Replication-defective vaccines are made from viruses that lack one or

Biological properties

The biological properties of HSV that control the course of human-HSV infection are: neuroinvasiveness—the ability to invade the brain; neurotoxicity—the ability to multiply and destroy the brain; and latency—the ability to remain in a non-replicating form in neurons of dorsal root ganglia and the autonomic nervous system. Although neuroinvasiveness and neurotoxicity seem to be distinct characteristics, deletion of almost any HSV gene affects one or both properties but not the ability to

Epidemiology

HSV must contact mucosal surfaces or abraded skin to initiate infection. The type of HSV infection that results is a function of the host's immune status. Susceptible individuals (ie, those who are HSV seronegative) develop “primary” infection after their first exposure to HSV-1 or HSV-2. “Initial” infection occurs when an individual who has antibodies to either HSV-1 or HSV-2 is infected with the other virus type for the first time. HSV-1 and HSV-2 are usually transmitted by different routes

Diagnosis

Diagnosis can be confirmed by virus isolation in cell culture or PCR detection of HSV DNA. Cell culture is less expensive than PCR12 and provides a virus isolate that can be typed. A scraping of skin vesicles should be taken from any skin lesions and transferred in appropriate virus transport media, preferably on ice, to a diagnostic virology laboratory for inoculation onto a susceptible cell culture. Cytopathic effects usually develop 24–48 h after inoculation. Serological diagnosis of HSV

Signs and symptoms

The most common sites of HSV infection are skin and mucosal membranes, irrespective of virus type. The incubation period for HSV-1 or HSV-2 is about 4 days, and ranges from 2 to 12 days. Most people do not notice an HSV-1 or HSV-2 infection.8 Primary HSV-1 infection of the oropharynx and HSV-2 infection of the genital tract result in virus excretion for up to 23 days (average of around 7–10 days). Symptomatic oropharyngeal disease is characterised by lesions of the buccal and gingival mucosa

Drugs

Aciclovir, a synthetic acyclic purine-nucleoside analogue, is the standard therapy for HSV infections19 and has greatly helped control symptoms. Precursor drugs, valaciclovir (converted to aciclovir) and famciclovir (converted to penciclovir), have been licensed and have better oral bioavailability than aciclovir and penciclovir, respectively.20

Mucous membrane HSV infections

Initial genital or oral HSV infection can be treated with topical, oral, or intravenous aciclovir. Topical therapy is much less effective than oral or

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