Chapter 4 Viruses and prions
Viruses are one of the smallest forms of microorganism and infect most other forms of life: animals, plants and bacteria. They can also cause severe acute oral and orofacial disease, produce oral signs of systemic infection, and be transmitted to patients and dental staff. The main features that characterize viruses are:
Viruses consist of a nucleic acid core containing the viral genome, surrounded by a protein shell called a capsid (Figs 4.1 and 4.2). The entire structure is referred to as the nucleocapsid. This may be ‘naked’, or it may be ‘enveloped’ within a lipoprotein sheath derived from the host cell membrane. In many viruses (e.g. orthomyxoviruses, paramyxoviruses), the ensheathment begins by a budding process at the plasma membrane of the host cell, while others, such as herpesviruses, ensheath at the membrane of the nucleus or endoplasmic reticulum.
The protein shell or capsid consists of repeating units of one or more protein molecules; these protein units may go on to form structural units, which may be visualized by electron microscopy as morphological units called capsomeres (Fig. 4.1). Genetic economy dictates that the variety of viral proteins be kept to a minimum as viral genomes lack sufficient genetic information to code for a large array of different proteins. In enveloped viruses, the protein units, which comprise the envelopes and are visualized electron microscopically, are called peplomers (loosely referred to as ‘spikes’).
Viral nucleic acid may be either DNA or RNA. The RNA, in turn, may be ss or ds, and the genome may consist of one or several molecules of nucleic acid. If the genome consists of a single molecule, this may be linear or have a circular configuration. The DNA viruses all have genomes composed of a single molecule of nucleic acid, whereas the genomes of many RNA viruses consist of several different molecules or segments, which are probably loosely linked together in the virion.
In terms of volume, the major bulk of the virion is protein, which offers a protective sheath for the nucleic acid. The viral protein is made up of two or three different polypeptide chains, although in some only one kind of polypeptide chain may be present. Virion surface proteins may have a special affinity for receptors on the surface of susceptible cells and may bear antigenic determinants.
Although most viral proteins have a structural function, some have enzymatic activity. For instance, many viruses such as the human immunodeficiency virus (HIV) contain a reverse transcriptase, whereas several enzymes (e.g. neuraminidase, lysozyme) are found in larger, more complex viruses.
In general, lipids and carbohydrates of viruses are only found in their envelopes and are mostly derived from the host cells. About 50–60% of the lipids are phospholipids; most of the remainder is cholesterol.
Vertebrate viruses are classified into families, genera and species. The attributes used in classification are their symmetry, the presence or absence of an envelope, nucleic acid composition (DNA or RNA), the number of nucleic acid strands and their polarity. Classification of some of the recognized families of RNA and DNA viruses is given in Table 4.1. (Note: to memorize which viruses contain DNA, remember the acronym ‘PHAD’: P is for papova and pox, H for herpes and AD for adenoviruses. Most of the remainder are RNA viruses, including the self-evident picornaviruses.)
|Enveloped, double-stranded nucleic acid||Herpesviruses|
|Herpes simplex virus|
|Human herpesvirus 6|
|Hepatitis B virus|
|Human immunodeficiency viruses HTLV-I, -III|
HTLV-I, human T cell leukaemia virus type I.
Papovaviruses are small, icosahedral DNA viruses with a capacity to produce tumours in vivo and to transform cultured cell lines. The name ‘papova’ is an acronym derived from the papillomavirus, polyomavirus and vacuolating agent simian virus 40 (SV40), which make up this family.
This genus contains human serotypes that cause benign skin tumours or warts and both oral and skin papillomas (e.g. hand and plantar warts). Although they were regarded as a cosmetic nuisance rather than a specific disease, it is now known that the papillomaviruses may be involved in genital and oral cancers.
Adenoviruses are icosahedral DNA viruses, commonly associated with respiratory and eye infections in humans. These viruses were so named because they were first isolated from cultured adenoid tissue eliciting cytopathic effects. Syndromes associated with adenoviruses include:
These enveloped, icosahedral viruses are 180–200 nm in diameter and contain a linear dsDNA molecule. The Herpesviridae family has over 100 members spread widely among vertebrates, and invertebrates and new species are continuously being added. Herpesviruses are unstable at room temperature and are rapidly inactivated by lipid solvents such as alcohol and other common disinfectants owing to the disruption of the outer lipid envelope.
During reproduction, maturation of the progeny begins in the nucleus of the host cell, which buds through the nuclear membrane and acquires the viral envelope. Typical and highly pathognomonic intranuclear inclusions are therefore found in cells that have undergone active virus replication. As many herpesviruses can fuse with the cells they infect, polykaryocytes or giant cells readily appear in tissue lesions. Such cells, e.g. Tzanck cells or nuclear inclusions (Lipschiitz bodies), are hallmarks of herpetic infections.
Different herpesviruses cause a variety of infectious diseases, some localized and some generalized, often with a vesicular rash. Herpesviruses establish latent infection, which can be readily reactivated by immunosuppression (Table 4.2).
|Virus||Site of latency|
|Herpes simplex virus||Trigeminal ganglion|
|Varicella-zoster virus||Sensory ganglia|
|Epstein–Barr virus||Epithelial cells|
|Cytomegalovirus||Salivary gland cells|