There are numerous species of viruses that are capable of infecting humans and the organisms are primarily classified according to the type of nucleic acid present in their genome, that is, DNA or RNA viruses. However, other features such as the arrangement of the protein subunits surrounding the nuclear material, the size of the virion and whether the virion is naked or enveloped are useful in subdividing and speciating the viruses. Certain species of viruses show affinity for specific mammalian cells. This phenomenon, known as tissue tropism, is exemplified by herpes and hepatitis viruses, which replicate in epithelial cells and hepatocytes, respectively. Viruses that show tropism for oral and facial skin epithelium and elicit clinical manifestations in these regions include herpes simplex virus (I and II), varicella zoster virus and the Coxsackie viruses. All of these viruses share a common feature by producing vesiculoulcerative lesions in the oral and perioral regions, accompanied by lymphadenopathy. The papovavirus also infects oral epithelium but it produces papillary rather than vesiculobullous lesions. Cytomegalovirus and mumps virus demonstrate tropism for salivary gland tissue with sialadenopathy as the major clinical finding.
There are numerous species of viruses capable of infecting humans and the organisms are primarily classified according to the type of nucleic acid present in their genome, i.e. DNA or RNA viruses. However, other features such as the arrangement of the protein subunits (capsids) surrounding the nuclear material, the size of the virion and whether the virion is naked or enveloped are useful in subdividing and speciating the viruses (Table 10.1).
|Virus||Nucleic acid; configuration||Virus symmetry||Envelope||Approximate size (nm)|
|Human immunodeficiency virus||RNA; SS||Deltaicosahedron||Yes||100|
Certain species of viruses show affinity for specific mammalian cells. This phenomenon, known as tissue tropism, is exemplified by herpes and hepatitis viruses which replicate essentially in epithelial cells and hepatocytes respectively. Viruses that show tropism for oral and facial skin epithelium and elicit clinical manifestations in these regions include herpes simplex virus (I and II), varicella zoster virus and the Coxsackie viruses. All of these viruses share a common feature by producing vesiculoulcerative lesions in the oral and perioral regions, usually accompanied by lymphadenopathy (Table 10.2). The papovavirus (e.g. papillomavirus) also infects oral epithelium but it produces papillary rather than vesiculobullous lesions. Cytomegalovirus and mumps virus demonstrate tropism for salivary gland tissue with sialadenopathy as the major clinical finding.
|Herpes simplex I|
|Gingivostomatitis||Marginal gingivae and mucosae with vesicles and ulcers|
|Skin||Localized dermal eruptions|
|Ocular||Palpebral and bulbar conjunctiva|
|Eczema hepeticum (Kaposi’s varicelliform eruptions)||Generalized oral and dermal eruptions with pustule formation|
|Labialis||Vesicles on vermillion border|
|Intraoral||Clusters of small vesicles and ulcers on palatal gingiva or mandibular gingiva|
|Primary (chickenpox)||Trunk and face with a few isolated oral vesicles|
|Secondary (shingles)||Unilateral vesicles stopping at midline and following the distribution of branches of Vth cranial nerve|
|Coxsackie virus, group A|
|Herpangina||Soft palate and faucial pillars|
|Hand, foot and mouth disease||Movable mucosa, arms below elbows, legs below knees|
|Measles||Punctate microulcers near parotid duct orifice (Koplik’s spots) 2–3 days prior to rash|
|Mumps||Unilateral or bilateral parotid swelling|
When a virus comes into contact with a host cell one of a number of host–parasite interactions may occur. Firstly, the host cell may not be susceptible to virus attack, e.g. only hepatocytes become infected with hepatitis B virus. Secondly, the host cell may be susceptible and viral infection occurs. In the first stage of infection the virus becomes attached to receptors on the cell surface and in entering the cell it usually becomes covered with part of the cell membrane. Once inside the cell, the protein coat of the virus is removed and the viral nucleic acid released for the production of viral mRNA. It is by means of mRNA that a virus takes over the biosynthetic properties of the host cell. Virus mRNA then attaches to cell ribosomes and directs the synthesis of virus-specific proteins. Subsequently new virus particles are assembled within the host and finally released from the cell, either slowly by extrusion (budding) through the cell membrane, or rapidly as a result of cell rupture. The host cell then dies, producing a cytopathic effect (CPE). The third possibility is that the cell becomes infected but not killed. The host cell becomes transformed (as a result of viral nucleic acid becoming incorporated in its genome) to one which possesses malignant properties, i.e. unrestrained, proliferative growth. The fourth possible interaction is when the cell becomes infected and the virus remains within the cell in a potentially active state (latency) but produces no obvious effect on cell functions. The virus can become activated by a range of stimuli at a later time, producing tissue damage, e.g. recurrent herpetic infections and shingles.
The defence mechanisms of the host react to virus infection in both a non-specific and a specific fashion. The non-specific mechanisms include: (1) mechanical and chemical factors, e.g. the washing action of saliva, swallowing and subsequent inactivation of sensitive viruses in gastric acid; (2) the phagocytic and killing activity of polymorphonuclear leucocytes and mononuclear phagocytes; and (3) the action of interferon (probably the most important factor in recovery from acute viral infection) which is a complex of ’protein regulating molecules’ which are released by virus infected cells. Interferon, a powerful inhibitor of virus replication, is then taken up by healthy cells which are rendered resistant to subsequent virus infection.
The specific defence mechanisms which are activated during viral infection are the humoral (antibody) and cell mediated (lymphokine production and T killer cells) responses. While antibodies are important in conferring long-term immunity to viral infection, their role in recovery from acute infection is uncertain, since patients with defects in their humoral immune response usually recover well from viral but not bacterial infections. Cell mediated immunity is important in recovery from acute infection, and patients with defects in cell mediated immunity often suffer from very severe bouts of common virus infections. A combination of (1) T lymphocytes which are cytotoxic for viral infected cells, and (2) lymphokine release which contains interferon and factors which attract, retain and activate macrophages at the site of infection, are involved in the cellular immune response.
Herpes simplex I, herpes simplex II, varicella zoster, Epstein–Barr virus and cytomegalovirus belong to the herpes group of viruses. Oral and perioral infections related to these viruses are described below.
Primary herpetic stomatitis is caused by herpes simplex virus and is the commonest viral infection affecting the mouth. While type I is most commonly isolated, type II, which in the past was thought to be confined to the genitalia, has been increasingly found in herpetic stomatitis. The incubation period is about five days and the virus is transmitted by direct contact with recurrent skin lesions or infected saliva. Children may carry the virus asymptomatically or as convalescent carriers in saliva for several months but the virus is rarely isolated in adults after the primary lesions heal. If infection occurs in early childhood, the disease is usually subclinical or mild, being dismissed as ’teething’, but if infection occurs in adults the symptoms are generally much more severe. In Western countries with a high standard of living, there is an increasing number of adult cases diagnosed, due to the absence of infection in childhood.
The clinical features of primary herpetic stomatitis consist of an initial stage where there is a mild to severe fever, enlarged lymph nodes and pain in the mouth and throat. Subsequently, variable numbers of vesicles develop haphazardly on the surface of the oral mucosa, although the tongue, buccal mucosa and gingiva are most commonly affected in primary gingivostomatitis. The vesicles quickly rupture to form small round or irregular superficial ulcers with erythematous haloes and greyish-yellow bases (Figure 10.1