Oral viral infections of adults.

The field of virology has advanced greatly over the past two decades, mainly because of the introduction of sophisticated molecular tools, such as monoclonal antibodies, polymerase chain reaction (PCR)-based amplification, DNA sequencing, DNA and protein microarray chip assays, and rapid diagnostic tests. These technologies have been the driving force in the identification of viral bodies, proteins and nucleic acids in body fluids and tissue samples, and in determining the host response to viral infections. The 5th (2007) edition of Fields Virology provides an indepth description of viral methodology and medical virology, and is an important source of reference for this review (118). Viruses replicate only when present within eukaryotic (animals, plants, protists and fungi) or prokaryotic (bacteria and archaea) cells, not on their own. The extracellular virion particle ranges in size from 20 to 300 nm and consists of either DNA or RNA contained within a protective protein capsid. Some viruses have an additional envelope comprising a lipid bilayer derived from the outer cellular membrane, the internal nuclear membrane, or the endoplasmic reticulum membrane of the infected cell. Taxonomically, viruses are classified according to the presence of DNA or RNA, single-stranded or double-stranded nucleic acid, and an enveloped or nonenveloped nucleocapsid. Additional taxonomical criteria include mode of replication, type of host, capsid shape, immunological properties and disease association. The host recognizes and reacts to the infecting virus by innate and adaptive immune responses. Important cells of the innate immune system include macrophages, dendritic cells and natural killer cells. Viruses activate inflammatory cell types to release antiviral cytokines and cytotoxic agents, and to induce lymphocyte-mediated adaptive immunity. A significant cytokine release is stimulated through activation of the tumor necrosis factor-a receptor ⁄ nuclear factor-jB ⁄ extracellular signal-regulated kinase pathway (49). Virally derived proteins, which are presented by major histocompatibility complex molecules on the surface of infected cells, serve as epitopes for specific host immune cells. Nonenveloped viruses are mainly controlled by the humoral adaptive immunity. Enveloped viruses are controlled by the cellular immunity through the action of natural killer cells and cytotoxic CD8 T lymphocytes. After recognizing viral surface antigens on infected cells, cytotoxic T lymphocytes inhibit virus replication by cytolytic killing and by releasing interferons, chemokines, tumor necrosis factor-a or other pro-inflammatory mediators. Viral disease may be a direct result of cell destruction or a secondary consequence of host immune reactions against viral proteins. Proinflammatory cytokines play important roles in the antiviral immune response, but interleukin-1b, interleukin-6 and tumor necrosis factor-a cytokines can also contribute to disease manifestation. The host usually performs a delicate balancing act between promoting antiviral cytokine responses and limiting the amount of tissue damage. To counteract the immune attack, viruses employ sophisticated immunoevasive strategies to suppress antiviral host responses. For example, some viruses produce proteins that alter the major histocompatibility complex and hence the exposure of viral proteins on the surface of infected cells. Viruses may encode viral homologs of host cytokines and decoy receptors capable of binding and neutralizing host-derived cytokines. A rapid rate of mutation in critical viral genes can help viruses avoid the adaptive host defense. Other viral gene products inhibit apoptosis, which facilitates a prolonged state of replication of infected cells and spread of the virus. Viral diseases of the oral mucosa and the perioral region are often encountered in dental practice, but have received only limited research interest. Viruses are important ulcerogenic and tumorigenic agents of the human mouth. The finding of an abundance of mammalian viruses in periodontitis lesions may suggest a role for viruses in more oral diseases than