The primary difference between viruses and other infectious agents is in the method of reproduction. Viruses do not divide as a means of propagation; they exist in two separate phases. Virions are virus particles that are complete, before contact with a host cell; at this phase, virions are infective. This particle consists of genetic information surrounded by a protein capsule. Upon contact with receptor sites of a suitable host cell, the virion injects its RNA or DNA into the cell, at which point it becomes a virus. The host cell's usual biosynthetic processes then cease and are directed to the replication of the virus [1]. New virions exit the cell and continue this pattern upon contact with another host cell. Transmission of viral diseases can occur via respiratory droplets, through direct contact of mucous membranes, and by the exchange of bodily fluids, such as blood and semen.

Viruses do not produce soluble toxins but cause damage by subverting the appropriate function of the host cell and by their own replication. The relationship between the CD4+ lymphocytes and HIV and that of the hepatitis virus subtypes and the hepatocytes are classic examples of viral damage at the cellular level that causes grave systemic consequences. Conventional mechanisms of antimicrobial therapy, such as the lysis of the cell walls of gram-positive bacteria and altered cell membrane permeability of fungal organisms by antifungal medications, do not apply to viruses. Antiviral medications can modify viral illnesses, but none are curative. Viral organisms can produce a vast array of problems, from the inconvenience associated with the common cold (caused by members of the adenovirus family) to the spectrum of devastating opportunistic infections seen in patients with HIV/AIDS. The problems of dental caries, periodontal disease, and odontogenic infections are of bacterial origin, while the fungal organism Candida albicans can cause oral fungal infections. Viruses can affect the oral and maxillofacial complex directly, such as HSV-1, or indirectly, as seen in immunosuppression among patients with HIV. While viral organisms are not responsible for common dental problems, these pathogens can create other systemic and oral problems and can be life-altering.

Hepatitis is essentially inflammation of the hepatocytes, the cells of the liver. Infectious hepatitis is associated with many different causes, including viruses, secondary syphilis, and extrapulmonary tuberculosis [2]. Noninfectious hepatitis can result from the prolonged use of medications prescribed for chronic illnesses and illicit drug and alcohol abuse. Among the infectious forms of hepatitis, acute viral hepatitis is the most common. Six hepatitis viruses have been identified to date: types A, B, C, D, E, and G, each of which belongs to a different viral family and has unique pathophysiologic features. Of these types, hepatitis G is less well understood and is not believed to be a significant source of disease in humans.

Hepatitis viruses replicate within the hepatocytes with a resultant cellular ballooning degeneration and necrosis. The long-term replacement of the hepatocytes with connective tissue is called cirrhosis. Symptoms of acute hepatitis can vary considerably and will depend upon the viral type and host response. Right upper-quadrant pain, nausea, vomiting, joint pain, and loss of appetite are among the possible presenting symptoms. Jaundice is relatively common among these patients as a result of accumulation of bilirubin, the degradation product of hemoglobin, in the plasma. The actual frequency of this sign varies, occurring in approximately 70% of hepatitis A infections, 30% of hepatitis B infections, and 25% in hepatitis C and E infections [3]. When liver disease is present, the conjugation of bilirubin with glucuronic acid and excretion into the intestine is impaired. The normal plasma concentration of bilirubin is less than 1 mg/100 mL; jaundice is defined as a concentration of 2.3 mg/100 mL or greater [4]. Complications from viral hepatitis can include cirrhosis, liver cancer, and fulminant hepatitis. Acute and rapid destruction of the hepatocytes and a resultant high mortality rate is characteristic of fulminant hepatitis. However distinctive these symptoms and complications may be, many patients infected with the hepatitis viruses have no symptoms. Among those with hepatitis A, 10% are asymptomatic, as are approximately 60% to 70% of patients with hepatitis B and 70% to 90% of patients with HCV [5].

Hepatitis viruses replicate within the hepatocytes with a resultant cellular ballooning degeneration and necrosis. The long-term replacement of the hepatocytes with connective tissue is called cirrhosis. Symptoms of acute hepatitis can vary considerably and will depend upon the viral type and host response. Right upper-quadrant pain, nausea, vomiting, joint pain, and loss of appetite are among the possible presenting symptoms. Jaundice is relatively common among these patients as a result of accumulation of bilirubin, the degradation product of hemoglobin, in the plasma. The actual frequency of this sign varies, occurring in approximately 70% of hepatitis A infections, 30% of hepatitis B infections, and 25% in hepatitis C and E infections [3]. When liver disease is present, the conjugation of bilirubin with glucuronic acid and excretion into the intestine is impaired. The normal plasma concentration of bilirubin is less than 1 mg/100 mL; jaundice is defined as a concentration of 2.3 mg/100 mL or greater [4]. Complications from viral hepatitis can include cirrhosis, liver cancer, and fulminant hepatitis. Acute and rapid destruction of the hepatocytes and a resultant high mortality rate is characteristic of fulminant hepatitis. However distinctive these symptoms and complications may be, many patients infected with the hepatitis viruses have no symptoms. Among those with hepatitis A, 10% are asymptomatic, as are approximately 60% to 70% of patients with hepatitis B and 70% to 90% of patients with HCV [5].

Interferon alfa-2b can result in many multisystemic side effects [14]. Potential oral effects include xerostomia, gingivitis, alteration in the sensation of taste, and paresthesia. A greater concern exists for the potential hematologic side effects. Thrombocytopenia, a condition in which the circulating platelet population is decreased, is an obvious concern for patients who require oral or periodontal surgery. Myelosuppression, specifically neutropenia, can reduce the number of neutrophils available. The potential for opportunistic oral infections, post-surgical infections, periodontal disease, and odontogenic infections increase. This medication can also increase the anticoagulant effect of warfarin if taken concurrently. Dental treatment for those who are receiving interferon alfa-2b should be limited to procedures directed toward the elimination of acute pain or odontogenic infections. The patient's physician should be consulted before any such procedure is initiated. Appropriate laboratory tests, such as a complete blood count (CBC) (to determine if platelets and leukocytes are within a safe range), should be completed prior to dental treatment. Additional tests to determine bleeding time may be required.

Another major function of the liver is the metabolism of medications such as local anesthetics, analgesics, antibiotics, and sedatives used in dental treatment. The metabolism of the amide local anesthetics, such as lidocaine, mepivacaine, etidocaine, and bupivacaine, occurs primarily in the liver [16]. Articaine, another amide anesthetic, is metabolized partially by the liver but also by plasma carboxylesterases. Analgesics such as aspirin, ibuprofen, and acetaminophen, alone or combined with narcotics such as codeine, hydrocodone, or oxycodone, also rely on hepatic metabolism. Similarly, antibiotics such as amoxicillin, ampicillin, clindamycin, and tetracycline utilize the liver for primary metabolism [3]. Before any of these medications are prescribed or administered to any patient with active hepatitis or chronic hepatitis infection, the patient's physician should be consulted. The current state of hepatic function must be assessed to determine the ability of the liver to metabolize the medications adequately. Dosages and the frequency of administration of any of the medications will require adjustments that correspond to the degree of the compromise of hepatic function.

There is no current vaccination against HCV. All healthcare professionals should adhere to standard precautions for infection control to minimize the risk of contracting this disease from percutaneous exposure or the accidental inoculation of unprotected body surfaces from infected patients' blood [18]. No specific oral lesions are characteristic of patients with HCV infection.

HSV-1 is responsible for the most frequently occurring viral oral lesions. An initial form, primary herpetic gingivostomatitis, occurs after infection with the virus, most often in children, and is characterized by painful oral ulcerations, fever, and flu-like symptoms. HSV-1 is not eliminated with the healing of these lesions but migrates to a regional nerve ganglion, where it can remain dormant for an extended period of time. The oral reactivation of HSV-1 is called recurrent herpes labialis, and these lesions more commonly referred to as "cold sores" or "fever blisters." The classic presentation of these lesions features small vesicles that coalesce to form larger vesicles and rupture to form shallow ulcers surrounded by an erythematous border. These lesions most frequently involve the skin adjacent to the lip with an extension onto the lip commonplace. The lesions of HSV-1 are local and circumscribed and will heal without scarring. Application of topical acyclovir to the infected area or the use of oral acyclovir, valacyclovir, or famciclovir for 5 to 10 days will accelerate the healing process [31].

Oral hairy leukoplakia lesions are caused by the reactivation and replication of Epstein-Barr virus within the epithelial cells [43]. The oral presentation features characteristic corrugated, white striations, most frequently on the lateral surfaces of the tongue. Occasional involvement of the dorsum of the tongue or the buccal mucosa is also possible. These adherent lesions are generally asymptomatic and can feature bilateral or unilateral involvement [41]. Large lesions may be traumatized by occlusion, sharp edges of teeth, partial denture attachments, or the acrylic extensions of complete dentures. Pain is usually not associated with oral hairy leukoplakia, and many lesions are discovered during routine clinical exams. Treatment with oral acyclovir will cause remission, but the lesions will reappear upon cessation of therapy. Valacyclovir and famciclovir have higher oral bioavailability than acyclovir and can be dosed less often but also do not eliminate the latent state of infection [41]. The lesions should not interfere with routine dental treatment. Because their appearance is simultaneous with decreasing immunocompetence, it is advisable to obtain a CBC and CD4+ levels before invasive procedures are planned.

Cytomegalovirus (CMV) is the largest virus to infect humans. Among every 100 adults in the United States, 50 to 80 are infected with CMV by the time they are 40 years of age [47]. CMV shares the characteristic of latency seen in other members of the herpes virus family and can be reactivated when conditions such as immunosuppression occur. Most patients who develop CMV-related pathology have a CD4+ lymphocyte count of 100 cells/mcL or less [34]. Oral manifestations can include ulcerations anywhere on the oral mucosa. These ulcerations are nonindurated with a "punched-out" appearance and a varying erythematous border [48]. They can be very painful and have an extended duration due to the heightened stage of immunosuppression at which CMV is reactivated.

Cutaneous and intra-oral lesions can occur and assume a variety of anatomical configurations. The palate is the most common site of intra-oral Kaposi sarcoma lesions, with the gingival tissues and tongue also exhibiting frequent occurrences. Lesions can vary in size as they extend from the tissue surface from which they originate [51]. Larger lesions can interfere with speech, mastication, proper oral hygiene, and the ability to wear partial or complete dentures. Extension into and subsequent destruction of the underlying alveolar bone is also possible.

A decrease in salivary flow can also result in the increased retention of plaque on the teeth and an increased susceptibility to caries and periodontal disease. Patients who develop xerostomia secondary to salivary gland enlargement should be advised to maintain meticulous oral hygiene and should have more frequent recall appointments. Chewing sugar-free gum can stimulate the production of saliva from some of the residual elements of the salivary glands and may help maintain oral hygiene.

There are more than 150 different genotypes that comprise the HPV family [58]. As opposed to the characteristic ballooning degeneration and cellular lysis that most viruses cause, members of the HPV family cause proliferation of the epithelial tissues that can result in a multitude of benign and malignant lesions [59]. Only a select few of the HPV genotypes have oral or facial patterns of distribution.

HPV genotypes 2 and 4 cause the common skin wart (verruca vulgaris) and may cause lesions within the oral cavity or, more frequently, near the skin of the lower lip. Nearly one-third of these intra-oral lesions occur on the hard and soft palates and the uvula [60]. The solitary lesions are usually asymptomatic, sessile, and not pedunculated. Patients who have skin warts around nail beds or on their fingers can transmit the HPV virus to the oral tissues by parafunctional habits, such as the biting of fingernails. Conservative surgical excision with the submission of the tissue specimen for histologic analysis is required to determine if there are any malignant aspects within the lesion. Recurrences are possible.

In a study of 5,046 specimens of head and neck squamous cell carcinomas, nearly 26% contained HPV varied genotypes, with the HPV-16 genotype being the most prevalent [69,22]. A separate study showed that the HPV-16 genotype is the causative agent for 90% of cases of HPV-associated oropharyngeal squamous cell carcinomas [22]. The presence of HPV was higher among oropharyngeal carcinomas (35.6%) than among squamous cell carcinomas that developed in the oral cavity (23.5%) [69]. However, the presence of HPV DNA within a biopsied specimen does not establish a definitive causal relationship. The development of any malignancy is the result of a combination of factors that can vary considerably among individuals. Most patients who develop premalignant or malignant lesions within the oral cavity and/or oropharyngeal regions have a history of tobacco use. However, an increasing number of patients with oral cancer have not used these products, and an exact etiology among them is unknown. HPV may be a consideration in the development of oral cancer, although its precise role as an oncogenic agent remains unknown. It has been suggested that HPV may reduce the ability of specific tumor suppressor genes to function properly, thereby facilitating the growth and proliferation of cancer cells.

The measles virus is one of several members of the RNA paramyxovirus group. Although children in the United States are inoculated against measles as part of the standard childhood immunization schedule (as a component of the measles-mumps-rubella [MMR] vaccine), outbreaks of this disease still occur. Approximately 10 million cases and 128,000 deaths occur worldwide annually [70]. Although most outbreaks occur in foreign countries or in unvaccinated adults returning from international travel, there is an increased risk associated with unvaccinated children [71]. Due to parental concerns regarding vaccine safety, an increasing number of children are not receiving measles vaccinations, despite a lack of scientific evidence linking the vaccine to adverse long-term effects, including autism [10; 71].

The measles can be spread easily to susceptible individuals via contaminated airborne respiratory droplets. A 7- to 10-day incubation period is followed by the development of a fever, cough, conjunctivitis, rhinitis, photophobia, and the characteristic red maculopapular rash. The rash typically begins on the forehead and behind the ears, then spreads to other areas of the body [72].

Oral manifestations of measles occur, but alone are not diagnostic for the disease. A common feature is the development of Koplik spots [72]. These small, white necrotic spots surrounded by an erythematous halo usually appear on the buccal mucosa with variable symptomatology. Mucosal ulcerations and gingivitis can also occur but are not an identifying feature of measles.

Treatment for measles is usually palliative and supportive [73,74]. Oral analgesics can decrease the discomfort and fever that accompanies the disease. Oral lesions can complicate mastication and swallowing, so softer foods and liquid nutritional supplements may be necessary. With supportive care, most patients recover completely. However, some will develop complications, such as encephalitis and secondary infections, that can have significant morbidity and even result in death. The World Health Organization and the CDC recommend that severe cases of measles in children be treated with vitamin A, administered immediately on diagnosis and repeated the next day [74,75].

Approximately 70% to 80% of affected patients have bilateral swelling of the parotid glands, while the remainder have unilateral swelling [77]. The submandibular and the sublingual salivary glands can also be infected, but rarely without simultaneous involvement of the parotid gland. Although unilateral or bilateral enlargement of the parotid glands is the most distinguishing feature of this disease, it is a systemic viral infection affecting the entire body. The nervous system, glandular tissue, and organs such as the liver, kidney, and pancreas can also be affected by the mumps virus [77,78].

Transmission occurs by direct contact or by the inhalation of viral-laden aerosolized droplets. The oral and maxillofacial manifestations of the mumps include facial swelling adjacent to the affected parotid glands and intra-oral swelling and erythema around the parotid duct, also known as Stensen duct [77]. Swelling of the parotid gland can cause trismus, or difficulty opening the mouth. Swelling and edema in the parotid region can place pressure and cause pain on the adjacent musculature that controls the functional movement of the jaws, such as during mastication.

Hand, foot, and mouth disease is usually caused by coxsackievirus A16, although other coxsackievirus genotypes can serve as etiologic agents [79,80]. The disease primarily affects children during the summer and early fall. It usually begins with fever, loss of appetite, fatigue, and sore throat, followed within one or two days by oral sores.

The oral lesions of hand, foot, and mouth disease feature vesicles that quickly rupture to form shallow ulcerations encircled by an erythematous halo. Any area of the oral mucosa can be affected, but lesions occur most often on the palate, tongue, and buccal mucosa. The lesions can be difficult to distinguish among other oral ulcerative lesions, such as aphthous ulcers. However, hand, foot, and mouth disease usually features similar cutaneous lesions on the hands and feet, although the lesions may be limited to cutaneous or oral manifestations in some cases. Afflicted patients are most contagious during the initial week of their infection. Coxsackievirus A16 remains for weeks after symptoms have dissipated, and the patient remains infectious to others during this time [80].

As noted, herpangina is caused by any one of the several genotypes of the coxsackievirus, not by a member of the herpesvirus family, as the name might suggest. This infection occurs most frequently in young children, but adults can also become infected. Patients develop a fever, sore throat, headache, and malaise. Infected salivary droplets are the primary means of transmission, but the fecal-oral route is also a possibility [81].

Vesicular eruptions associated with herpangina rupture to form shallow ulcerations with erythematous halos in the posterior aspect of the mouth. The soft palate, uvula, and tonsillar pillars and fauces are the common areas of involvement. This predilection for the posterior aspect of the mouth and oropharynx differentiates these lesions from aphthous ulcers and from hand, foot, and mouth disease, the lesions of which appear in all areas of the oral cavity [80].

Treatment is palliative and supportive. Herpangina lesions can be very painful, especially during swallowing. Patients may require a soft diet with liquid nutritional supplements. Analgesics may be required in a liquid formulation, as pills or capsules can be difficult to swallow, especially for children [80]. Acidic foods or beverages should be avoided. Immunity to a herpangina infection is limited to the coxsackievirus genotype that caused the infection. Ulcerations generally regress in approximately one week, and most patients recover quickly without systemic complications.