Effects of viral replication on host cells
Definitions
Cells that support viral replication are called permissive. Infections of permissive
cells are usually productive because infectious progeny virus is produced. Most
productive infections are called cytocidal (cytolytic) because they kill the host cell.
Infections of non-permissive cells yield no infectious progeny virus and are called
abortive. When the complete repertoire of virus genes necessary for virus replication
is not transcribed and translated into functional products the infection is referred to
as restrictive. In persistent and in some transforming infections, viral nucleic acid
may remain in specific host cells indefinitely; progeny virus may or may not be
produced.
Cytocidal Infections
Infection by cytocidal viruses is usually associated with changes in cell morphology,
in cell physiology and sequential biosynthetic events. Many of these changes are
necessary for efficient virus replication.
Morphologic Effects: The changes in cell morphology caused by infecting virus are
called cytopathic effects (CPE). Common examples are rounding of the infected cell,
fusion with adjacent cells to form a syncytium (polykaryocytes), and the appearance
of nuclear or cytoplasmic inclusion bodies. Inclusion bodies may represent either
altered host cell structures or accumulations of viral components.
Effects on Cell Physiology: The interaction of virus with the cell membrane and/or
subsequent events, (for example, synthesized viral proteins) may change the
physiological parameters of infected cells, including movement of ions, formation
of secondary messengers, and activation cascades leading to altered cellular
activities.
Effects on Cell Biochemistry: Many viruses inhibit the synthesis of host cell
macromolecules, including DNA, RNA, and protein. Viruses may also change
cellular transcriptional activity, and protein-protein interactions, promoting efficient
production of progeny virus. For some viruses, specific cellular biochemical
functions may be stimulated in order to enhance virus replication.
Genotoxic Effects: Following virus infection, breakage, fragmentation,
rearrangement and/or changes in the number of chromosomes may occur.
Biologic Effects: Virus-specified proteins may alter the cell's antigenic or immune
properties, shape, and growth characteristics.
Persistent Infections
Some viruses evolved the ability to remain in specific cells for long periods of time.
These infections include: latent, chronic, and slow virus infections. The type of
persistent infection usually influences the extent of cellular changes.
Latent Infection: Latent infections are characterized by restricted expression of the
episomal or integrated virus genome. The viral genomic product(s) are associated
with few, if any, changes in the latently infected cell.
Chronic Infection: The cellular effects of chronic infection are usually the same as
those of acute cytocidal infections, except that production of progeny may be slower,
intermittent or limited to a few cells. The long-term cellular changes may result in
severe disease, immune suppression or may trigger immune responses to damaged,
or undamaged cells or tissues.
Slow Infection: This type of virus-cell interaction is characterized by a prolonged
incubation period, without significant morphological and physiological changes of
infected cells. A slow progression of cellular injury may take years and is followed
by extensive cellular injury and disease.
Transforming Infections
DNA or RNA tumor viruses may mediate multiple changes that convert a normal
cell into a malignant one. RNA tumor viruses usually transform cells to a malignant
phenotype by integrating their own genetic material into the cellular genome and
may also produce infectious progeny. DNA tumor virus infections are often
cytocidal; thus transformation is associated with abortive or restrictive infections in
which few viral genes are expressed.
Stages of Transformation: Transformation involves at least two processes: first, the
cell gains the capacity for unlimited cell division (immortalization), and second, the
immortalized cells acquire additional heritable genetic changes by which the cell is
able to produce a tumor in an appropriate host.
Mechanisms of Oncogenic Transformation:
