Introduction to Virology
Epidemiologic
studies show that viral
infections in developed countries
are the most common cause of acute disease that does not require
hospitalization. In developing
countries, viral diseases also exact a heavy toll in mortality and permanent disability,
especially among infants and children.
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.
Ferdinando Dianzani
Thomas Albrecht
Samuel Baron
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