11.01
Rafless bencoolen
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Emerging viral diseases such as those due to HIV, ebolavirus and hantavirus, appear regularly. Now that antibiotics effectively control most bacterial infections, viral infections pose a relatively greater and less controlled threat to human health. Some data suggest that the already broad gamut of established viral diseases soon may be expanded to include other serious human ailments such as juvenile diabetes, rheumatoid arthritis, various neurologic and immunologic disorders, and some tumors.
Viruses can infect all forms of life (bacteria, plants, protozoa, fungi, insects, fish, reptiles, birds, and mammals); however, this section covers only viruses capable of causing human infections. Like other microorganisms, viruses may have played a role in the natural selection of animal species. A documented example is the natural selection of rabbits resistant to virulent myxoma virus during several epidemics deliberately induced to control the rabbit population in Australia. Indirect evidence suggests that the same selective role was played by smallpox virus in humans. Another possible, though unproved, mechanism by which viruses may affect evolution is by introducing viral genetic material into animal cells by mechanisms similar to those that govern gene transfer by bacteriophages. For example, genes from avirulent retrovirus integrated into genomes of chickens or mice produce resistance to reinfection by related, virulent retroviruses. The same relationship may exist for human retroviruses, since human leukemia-causing retroviruses have been reported.
Viruses are
- small,
- subcellular agents
- that are unable to multiply outside a host cell (intracellular, obligate parasitism).
- The assembled virus (virion) is formed to include only one type of nucleic acid (RNA or DNA)
- and, in the simplest viruses, a protective protein coat.
- The nucleic acid contains the genetic information necessary to program the synthetic machinery of the host cell for viral replication.
- The protein coat serves two main functions:
1. first, it protects the nucleic acid from extracellular environmental insults such as nucleases;
2. second, it permits attachment of the virion to the membrane of the host cell, the negative charge of which would repel a naked nucleic acid. Once the viral genome has penetrated and thereby infected the host cell, virus replication mainly depends on host cell machinery for energy and synthetic requirements.
The various virion components are synthesized separately within the cell and then assembled to form progeny particles. This assembly type of replication is unique to viruses and distinguishes them from all other small, obligate, intracellular parasites. The basic structure of viruses may permit them to be simultaneously adaptable and selective.
- Many viral genomes are so adaptable that once they have penetrated the cell membrane under experimental conditions, viral replication can occur in almost any cell.
- On the other hand, intact viruses are so selective that most virions can infect only a limited range of cell types. This selectivity exists largely because penetration of the nucleic acid usually requires a specific reaction for the coat to attach to the host cell membrane and some specific intracellular components.
Although some viruses may establish some forms of silent infection of cells, their multiplication usually causes cell damage or death; however, since viruses must depend on host survival for their own survival, they tend to establish mild infections in which death of the host is more an aberration than a regular outcome. Notable exceptions are HIV, ebolavirus, hantavirus and rabiesvirus.
Viruses are distinct among microorganisms in their extreme dependence on the host cell.
- Since a virus must grow within a host cell, the virus must be viewed together with its host in any consideration of pathogenesis, epidemiology, host defenses, or therapy.
- The bilateral association between the virus and its host imposes specific conditions for pathogenesis. For example, rhinoviruses require a temperature not exceeding 34°C; this requirement restricts their growth to only those cells in the cool outer layer of the nasal mucosa, thereby preventing spread to deeper cells where temperatures are higher.
The intracellular location of the virus often protects the virus against some of the host's immune mechanisms; at the same time, this location makes the virus vulnerable because of its dependence on the host cell's synthetic machinery, which may be altered by even subtle physical and chemical changes produced by the viral infection (inflammation, fever, circulatory alterations, and interferon).
Epidemiologic properties depend greatly on the characteristics of the virus-host association. For example, some arthropod-borne viruses require a narrow range of temperature to multiply in insects; as a result, these viruses are found only under certain seasonal and geographic conditions. Other environmental conditions determine the transmissibility of viruses in aerosols and in food.
Viruses are difficult targets for chemotherapy because they replicate only within host cells, mainly utilizing many of the host cell's biosynthetic processes. The similarity of host-directed and virus-directed processes makes it difficult to find antiviral agents specific enough to exert a greater effect on viral replication in infected cells than on functions in uninfected host cells. It is becoming increasingly apparent, however, that each virus may have a few specific steps of replication that may be used as targets for highly selective, carefully aimed chemotherapeutic agents. Therefore, proper use of such drugs requires a thorough knowledge of the suitable targets, based on a correct diagnosis and a precise understanding of the replicative mechanisms for the offending virus.
- Knowledge of the pathogenetic mechanisms by which virus enters, spreads within, and exits from the body also is critical for correct diagnosis and treatment of disease and for prevention of spread in the environment.
- Effective treatment with antibody-containing immunoglobulin requires knowing when virus is susceptible to antibody (for example, during viremic spread) and when virus reaches target organs where antibody is less effective.
- Many successful vaccines have been based on knowledge of pathogenesis and immune defenses.
- Comparable considerations govern treatment with interferon.
Clearly, viral infections are among the most difficult and demanding problems a physician must face. Unfortunately, some of these problems still lack satisfactory solutions, although tremendous progress has been made during the last several decades. Many aspects of medical virology are now understood, others are being clarified gradually, and many more are still obscure. Knowledge of the properties of viruses and the relationships they establish with their hosts is crucial to successful investigation and clinical management of their pathologic processes.
Our plan for conveying this knowledge is to present, first, concepts of viral structure, and then relate them to principles of viral multiplication. Together these concepts form the basis for understanding how viruses are classified, how they affect cells, and how their genetic system functions. These molecular and cellular mechanisms are combined with the concepts of immunology to explain viral pathogenesis, nonspecific defenses, persistent infections, epidemiology, evolution, and control. The important virus families are then discussed individually. Having studied the virology section, the reader should be able to use many principles of virology to explain individual manifestations of virus infection and the processes that bring them about.
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