Herpesvirus Infections

Herpesvirus infections are diseases caused by members of the family Herpesviridae, a group of large enveloped DNA viruses that share the defining capacity to establish lifelong latency after primary infection and to reactivate later. The eight human herpesviruses include herpes simplex viruses 1 and 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesviruses 6, 7, and 8.

Definition

Herpesvirus infections (MeSH: Herpesviridae Infections) are infections caused by viruses of the family Herpesviridae, characterized by an initial (primary) infection followed by lifelong latency in host cells and the potential for clinical reactivation.

Scope

This topic covers the human herpesviruses as a family, their hallmark biology of latency and reactivation, the major clinical syndromes (orolabial and genital herpes, chickenpox and shingles, infectious mononucleosis, congenital and opportunistic cytomegalovirus disease, and herpesvirus-associated malignancies), transmission, and diagnosis. It is reference-educational and does not provide antiviral dosing or individualized management.

Core questions

• Which human herpesviruses exist and what clinical syndromes does each cause?
• What is the biological basis of herpesvirus latency and reactivation?
• How do herpesvirus infections behave differently in immunocompetent versus immunocompromised hosts?
• How are primary, latent, and reactivated herpesvirus infections diagnosed?

Key concepts

• Family Herpesviridae and the eight human herpesviruses
• Latency and reactivation
• Herpes simplex virus 1 and 2
• Varicella-zoster virus (chickenpox and herpes zoster)
• Epstein-Barr virus and infectious mononucleosis
• Cytomegalovirus (congenital and opportunistic disease)
• Herpesvirus-associated malignancy (EBV, HHV-8)
• Disease in the immunocompromised host

Mechanisms

After primary infection at a mucosal or epithelial site, herpesviruses travel to and persist in specific host cells in a latent state in which the viral genome is maintained with limited gene expression: herpes simplex and varicella-zoster viruses become latent in sensory ganglia, while Epstein-Barr virus persists in B lymphocytes and cytomegalovirus in myeloid lineage cells. Periodic reactivation, often precipitated by stress, immunosuppression, or other triggers, leads to renewed replication and recurrent or disseminated disease, with severity strongly dependent on host immune competence (whitley-roizman-2001; cohen-2000).

Clinical relevance

Herpesvirus infections are extremely common, with most adults carrying several of these viruses for life. Clinical importance ranges from troublesome recurrent mucocutaneous disease to severe outcomes such as herpes simplex encephalitis, congenital cytomegalovirus disease, and herpesvirus-associated cancers, with particular risk in newborns and immunocompromised patients. This entry describes the disease category and is not a basis for individual antiviral therapy.

Epidemiology

Seroprevalence of the human herpesviruses is high worldwide and generally rises with age; herpes simplex viruses, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus are among the most widely distributed human pathogens (whitley-roizman-2001; cohen-2000). Because latency is lifelong, the population reservoir is effectively permanent, and reactivation disease is concentrated in the very young, the elderly, and the immunosuppressed.

History

The herpesviruses were progressively defined through the twentieth century as the family of agents sharing latency, with herpes simplex virus among the earliest characterized. Epstein-Barr virus was discovered in 1964 in association with Burkitt lymphoma, establishing the first human tumour virus link for the family, and cytomegalovirus and the later-numbered human herpesviruses were subsequently delineated. The reference synthesis of herpesvirology is provided in Fields Virology (fields-virology; roizman-knipe-herpes).

Seminal works

• whitley-roizman-2001
• cohen-2000

Frequently asked questions

Can a herpesvirus infection ever be fully cleared from the body?

No; the defining feature of the herpesviruses is lifelong latency, so once primary infection occurs the virus persists in host cells for life, even when no symptoms are present and replication is controlled.

Why are herpesvirus infections especially dangerous in immunocompromised people?

Control of latent herpesviruses depends heavily on cellular immunity; when immunity is impaired the viruses can reactivate and disseminate, producing severe organ disease that is uncommon in immunocompetent hosts.