HERPES VIRUS

The Herpesviridae are a large family of DNA viruses that cause diseases in humans and animals. The family name is derived from the Greek word herpein ("to creep"), referring to the latent, re-occurring infections typical of this group of viruses. Herpesviridae can cause latent or lytic infections.

Herpes Simplex - An acute, self-limited eruption of clustered vesicles, often with secondary crusting, caused by herpesvirus type 1 or type 2 infection.

Vesicles are located on an erythematous base on keratinized skin or mucous membranes. The most common areas of herpes simplex virus (HSV) type 1 eruptions are the vermilion, or red, borders of the lips and the external nares. The most common areas of HSV type 2 are the external genitalia and perianal areas. However, HSV vesicles can occur anywhere on the skin, mucus membranes, or cornea. Primary infection with the HSV type 1 usually occurs during childhood, and can manifest as fever, headache, regional adenopathy, and gingivostomatitis. Eruptions are usually recurrent, preceded by a prodrome of localized burning and/or pruritus over the site that will develop vesicles within 24 hours. An outbreak of herpes simplex typically lasts around 1 week. HSV is transmitted to others via physical contact, and can be shed subclinically when the host is asymptomatic. Viral replication in and lysis of epidermal cells leads to vesicle formation and local inflammation. The virus remains latent within sensory nerve ganglia for the life of the patient, and can be reactivated following physical trauma, ultraviolet light exposure, menstruation, or fever. Severe complications of HSV infections are rare. Any non-healing ulcer in an immunocompromised host should be evaluated for HSV.

Infections by HSV1, HSV2 and VZV are indistinguishable on routine microscopy. Keratinocytes are enlarged and acantholytic, with resultant formation intraepidermal vesicles and bullae. There is necrosis involving surface epithelium and sometimes involves hair follicles and sebaceous glands. A dense inflammatory infiltrate is often present in the dermis, and extends into the epidermis. The viruses cause typical morphologic changes in the nucleus, most often seen in the epidermis or follicular epithelium: there is multinucleation, molding of nuclei (i.e. closely approximated nuclei that conform to one another’s shape), margination of chromatin along the nuclear envelope (as if the nuclear outline has been highlighted with a marker). Oftentimes the nuclei have a characteristic steel gray color.

The human herpesviruses all share some common properties. One shared property is virus structure - all herpesviruses are composed of relatively large double-stranded, linear DNA genomes encoding 100-200 genes encased within an icosahedral protein cage called the capsid which is itself wrapped in a lipid bilayer membrane called the envelope. This particle is known as the virion.

Following binding of viral envelope glycoproteins to cell membrane receptors, the virion is internalized and dismantled, allowing viral DNA to migrate to the cell nucleus. Within the nucleus, replication of viral DNA and transcription of viral genes occurs. During symptomatic infection, infected cells transcribe lytic viral genes. In some host cells, a small number of viral genes termed latency associated transcript (LAT) accumulate instead. In this fashion the virus can persist in the cell (and thus the host) indefinitely. Reactivation of latent viruses has been implicated in a number of organic diseases. While primary infection is often accompanied by a self-limited period of clinical illness, long-term latency is symptom-free. Following activation, transcription of viral genes switches from LAT to multiple lytic genes that lead to enhanced replication and virus production. Often, lytic activation leads to cell death. Clinically, lytic activation is often accompanied by emergence of non-specific symptoms such as low grade fever, headache, sore throat, malaise, and rash as well as clinical signs such as swollen or tender lymph nodes and immunological findings such as reduced levels of natural killer cells.