Viruses were first described as “filterable agents” because their small size allowed them to pass through filters designed to retain bacteria. Unlike most bacteria, fungi, and parasites, viruses are obligate intracellular parasites that depend on the biochemical machinery of the host cell for replication. In addition, reproduction of viruses occurs by assembly of individual components rather than by binary fission.
Structure and Function
The simplest viruses consist of a genome of DNA or RNA (not both) packaged in a protective shell of protein and sometimes a membrane. Viruses lack the capacity to make energy or substrates, cannot make their own proteins, and cannot replicate independent of the host cell.
Viruses are approximately 100 to 1,000 fold smaller than the cells they infect. The smallest viruses (parvoviruses) are approximately 20 nanometers (nm) in diameter (1nm = 10-9 meters), whereas the largest animal viruses (poxviruses) overlap the size of the smallest bacterial cells (Chlamydia and Mycoplasma) having a diameter of approximately 300 nm.
All true viruses have a nucleic acid genome on the inside of a protein shell called a capsid. The capsid is a rigid structure able to withstand harsh environmental conditions. Some viruses are further packaged into a lipid membrane or envelope that is usually acquired from the cytoplasmic membrane of the infected cell and can be maintained only in aqueous solutions.
The envelope is readily disrupted by drying, acidic conditions, detergents, and solvents such as ether, resulting in the inactivation of the virus. As a result, enveloped viruses must remain wet and are generally transmitted in fluids, respiratory droplets, blood, and tissue. Most cannot survive the harsh conditions of the gastrointestinal tract.
Viruses with naked capsids (un-encapsulated) are generally more resistant to drying, acid, and detergents, including the acid and bile of the enteric tract. Many of these viruses are transmitted by the fecal-oral route and can endure transmission even in sewage.
Capsid structure is symmetrical and most commonly helical or icosahedral. Helical structures appear as rods, whereas the icosahedron is an approximation of a sphere assembled from symmetrical subunits.
Classification of Viruses
Traditionally, virus classification has been less than orderly! Viruses range from the structurally simple and small parvoviruses and picornaviruses to the large and complex poxviruses and herpesviruses. Their names may describe viral characteristics, the diseases they are associated with or even the tissue or geographical locale where they were first identified. Names such as picornavirus (pico, meaning small; rna, ribonucleic acid [RNA]: virus). The name retrovirus refers to the virus directed synthesis of DNA from an RNA template. Herpes virus is associated with the clinical infection Herpes simplex. Hepatitis virus refers to viruses that infect the liver. Coxsackie virus is named after a town in New York State.
Large efforts have been made in recent years to standardize virus classification. The International Committee on Taxonomy of Viruses (ICTV) has been instrumental in the process and new viruses are named according to their conventions. The ICTV’s Universal System of Virus Taxonomy strives to instil order into Order, Family, Sub-family, Genus, Species structure. Still medically important viruses tend to be referred to by their “vernacular” historic names. For more information on the classification of viruses and superb visual images look at the Big Picture Book of Viruses.
Viruses attach to cells that possess specific receptors and are then internalized. This initial contact occurs mainly in the respiratory tract, gastrointestinal tract, contact skin or genital tract. The virus may multiply locally and cause disease there (Rhinovirus and the common cold). Some spread from a local entry site hematogenously to have general effects or target specific organs e.g. hepatitis viruses.
The incubation period is the time between exposure to virus and onset of disease. During this usually asymptomatic period implantation, local multiplication and spread (for disseminated infections) occur.
Certain viruses are known to be associated with cancers e.g. Hepatitis B & C – hepatocellular carcinoma, Epstein-Barr virus – Burkitt’s lymphoma, Human papillomaviruses – Cervical cancer
Prions are unique and frightening infectious agents sometimes referred to as “slow viruses”. They appear to be proteins that can replicate themselves, which is contrary to the dogma of nucleic acids being the sole genetic material. They cause degenerative CNS disease in many animals including man. Sporadic Creutzfeldt-Jakob disease(CJD) has a worldwide incidence of one per million. It is a rapidly progressive degenerative brain disease that usually occurs in later life. Prion associated diseases have a very long incubation period and no demonstrable inflammatory or immune response. Much alarm has been raised recently over Bovine Spongiform Encephalopathy (“Mad Cow Disease”) in Great Britain and the transmissibility of the responsible prion to man. The resultant disease effects younger people and is distinguished from “classic” or “sporadic” CJD pathologically. It is referred to as “New Variant” CJD.
Identification of Viruses
A wide variety of viral investigations are available and the laboratory is dependent on the physician to make an accurate clinical diagnosis, ascertain the necessity of a laboratory investigation and to submit adequately obtained specimens promptly.
There are several basic methods of identifying viruses, some old and others very recent. The laboratory may use any of these investigations depending on the nature of the virus and the technology available. Generally there are five approaches in the laboratory determination of viral infection:
Detection of viral inclusions or other pathologic alterations – Intranuclear inclusions may be seen in cells by simple stained pathological preparations.
Culture of Viruses – Some viruses may be cultivated in cell cultures producing characteristic cytopathic effects. Special techniques such as fluorescent antibody staining utilizing specific anti-viral antibodies are sometimes used to get results faster.
Direct Detection of Virus – Viruses may be seen directly with electron microscopy which often complements histopathologic assessment.
Antigen Detection – Viral antigens are detected using a variety of immunologic techniques such as fluorescent antibody stains or enzyme linked immunoassays.
Nucleic Acid Detection – Many newly developed techniques ascertain the presence of viruses by identifying unique DNA or RNA sequences directly or after amplification by techniques such as the Polymerase Chain Reaction (PCR).
Serology – The demonstration of IgG and IgM antibodies is possible for many viral infections and is often the only practical means of diagnosis.
Control of Viral Infectious Diseases
- Active — vaccination The widespread use of vaccines is most important strategy to control disease ever devised.
- Passive — administration of immune globulins (antibodies) Used in specific circumstances to prevent disease before or after known exposure. Examples include Hepatitis B immune globulin, Rabies immune globulin, Tetanus Immune globulin.
Sanitation and Vector control
Sanitation is extremely important in the control of fecal-orally transmitted viruses such as enteroviruses, in particular poliovirus. Arboviruses (arthropod-borne viruses) such as West Nile virus are controlled by limiting their vectors.
Antiviral antibiotics are used both to treat and to prevent infection. An example is acyclovir for the therapy or prevention of Herpes simplex virus. Active therapy of HIV infection is associated with reduced transmission.
An example of the use of immune modulation as specific therapy. Examples include the therapy of Hepatitis C virus and some Human papillomavirus infections.