Herpes simplex virus
Wednesday 11 June 2003
UI:932 - Cutaneous herpes
scrotal skin : combined herpes simplex virus and Gram + cocci in chains
Multinucleation, molding and margination of chromatin in herpetic skin infection
HSV infected cells
Herpetic Cervicitis by Ed Euthman.
- Infected cells are multinucleate, with nuclear molding, nuclear enlargement, and glassy chromatin texture.
HSV-1 and HSV-2 differ serologically but are genetically similar and cause a similar set of primary and recurrent infections.61 These viruses produce acute and latent infections. Both viruses replicate in the skin and the mucous membranes at the site of entrance of the virus (usually oropharynx or genitals), where they produce infectious virions and cause vesicular lesions of the epidermis.
The viruses spread to sensory neurons that innervate these primary sites of replication. Viral nucleocapsids are transported along axons to the neuronal cell bodies, where the viruses establish latent infection. During latency, the viral DNA remains within the nucleus of the neuron, and only latency-associated viral mRNAs (called LATs or latency-associated transcripts) are synthesized.
In this state, no viral proteins appear to be produced, thus allowing the virus to evade immune recognition. In immunocompetent hosts, primary HSV infection resolves in a few weeks, although the virus remains latent in nerve cells. Reactivation of HSV-1 and HSV-2 may occur repeatedly with or without symptoms, and results in the spread of virus from the neurons to the skin or to mucous membranes.
Reactivation from latency occurs in the presence of host immunity, and herpesviruses have developed ways to avoid immune recognition. Herpes simplex viruses can evade antiviral CTL by inhibiting the MHC class I recognition pathway, and elude humoral immune defenses by producing receptors for the Fc domain of immunoglobulin and inhibitors of complement.
In addition to causing cutaneous lesions, HSV-1 is the major infectious cause of corneal blindness in the United States; corneal epithelial disease is thought to be due to direct viral damage, while corneal stromal disease appears to be immune mediated.
HSV-1 is also the major cause of fatal sporadic encephalitis in the United States, when the virus spreads to the brain, particularly the temporal lobes and orbital gyri of the frontal lobes. In addition, neonates and individuals with compromised cellular immunity (e.g., secondary to HIV infection or chemotherapy) may suffer disseminated herpesvirus infections.
All HSV lesions are marked by formation of large, pink to purple intranuclear inclusions (Cowdry type A) that contain intact and disrupted virions and push darkly stained host cell chromatin to the edges of the nucleus (Fig. 8-12). Although cell and nuclear size increase only slightly, herpesvirus produces inclusion-bearing multinucleated syncytia.
HSV-1 and HSV-2 cause lesions ranging from self-limited cold sores and gingivostomatitis to life-threatening disseminated visceral infections and encephalitis. Fever blisters or cold sores favor the facial skin around mucosal orifices (lips, nose), where their distribution is frequently bilateral and independent of skin dermatomes. Intraepithelial vesicles (blisters), which are formed by intracellular edema and ballooning degeneration of epidermal cells, frequently burst and crust over, but some may result in superficial ulcerations.
Gingivostomatitis, which is usually encountered in children, is caused by HSV-1. It is a vesicular eruption extending from the tongue to the retropharynx and causing cervical lymphadenopathy. Swollen, erythematous HSV lesions of the fingers or palm (herpetic whitlow) occur in infants and, occasionally, in health care workers.
Genital herpes is usually caused by HSV-2, but HSV-1 can also cause genital lesions. Genital herpes is characterized by vesicles on the genital mucous membranes as well as on the external genitalia that are rapidly converted into superficial ulcerations, rimmed by an inflammatory infiltrate (Chapter 22). Herpesvirus (usually HSV-2) can be transmitted to neonates during passage through the birth canal of infected mothers. Although HSV-2 disease in the neonate may be mild, more often it is fulminating with generalized lymphadenopathy, splenomegaly, and necrotic foci throughout the lungs, liver, adrenals, and central nervous system.
Two forms of corneal lesions are caused by HSV. Herpes epithelial keratitis shows typical virus-induced cytolysis of the superficial epithelium and is sensitive to antiviral drugs. In contrast, herpes stromal keratitis shows infiltrates of mononuclear cells around keratinocytes and endothelial cells, leading to neovascularization, scarring, opacification of the cornea, and eventual blindness. This is an immunologic reaction to the HSV infection and responds to corticosteroid therapy.
Herpes simplex encephalitis
Disseminated skin and visceral herpes infections
Disseminated skin and visceral herpes infections are usually encountered in hospitalized patients with some form of underlying cancer or immunosuppression.
Kaposi varicelliform eruption is a generalized vesiculating involvement of the skin, whereas eczema herpeticum is characterized by confluent, pustular, or hemorrhagic blisters, often with bacterial superinfection and viral dissemination to internal viscera.
Herpes esophagitis is frequently complicated by superinfection with bacteria or fungi. Herpes bronchopneumonia, which may be introduced with an airway inserted through oral herpes lesions, is often necrotizing, and herpes hepatitis may cause liver failure.
KSHV/HHV8 is implicated in the pathogenesis of Kaposi sarcoma. KSHV encodes proteins that can evade host immune defenses, disrupt cell cycle regulation, inhibit apoptosis, and affect intracellular signal transduction.
Herpes simplex virus infection (Animated)