Page 255 - Review of Medical Microbiology and Immunology ( PDFDrive )

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Genetics & Gene Therapy 30
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CHAPTER C ONTENT S

Introduction
Self-Assessment Questions
Mutations
Interactions Between Viruses
Practice Questions: USMLE & Course Examinations
Gene Therapy & Recombinant Vaccines
Gene Therapy
Recombinant Vaccines

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mebooksfree.com mebooksfree.com mebooksfree.com determining the function of viral genes. These mutations mebooksfree.com
Conditional lethal mutations are extremely valuable in
INTRODUCTION
The study of viral genetics falls into two general areas:
function normally under permissive conditions but fail to
(1) mutations and their effect on replication and pathogen-
replicate or to express the mutant gene under restrictive
esis; and (2) the interaction of two genetically distinct
conditions. For example, temperature-sensitive condi-
viruses that infect the same cell. In addition, viruses serve
tional lethal mutants express their phenotype normally at a
as vectors in gene therapy and in recombinant vaccines,
low (permissive) temperature, but at a higher (restrictive)
two areas that hold great promise for the treatment of
temperature, the mutant gene product is inactive. To give a
genetic diseases and the prevention of infectious diseases.
specific example, temperature-sensitive mutants of Rous
sarcoma virus can transform cells to malignancy at the
permissive temperature of 37°C. When the transformed
MUTATIONS
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phenotype reverts to normal appearance and behavior. The
Mutations in viral DNA and RNA occur by the same pro-
malignant phenotype is regained when the permissive tem-
cesses of base substitution, deletion, and frameshift as those
described for bacteria in Chapter 4. Probably the most
perature is restored.
important practical use of mutations is in the production of
Note that temperature-sensitive mutants have now
entered clinical practice. Temperature-sensitive mutants of
vaccines containing live, attenuated virus. These attenuated
influenza virus are now being used to make a vaccine,
mutants have lost their pathogenicity but have retained
their antigenicity; therefore, they induce immunity without
because this virus will grow in the cooler, upper airways
where it causes few symptoms and induces antibodies, but
causing disease.
it will not grow in the warmer, lower airways where it can
There are two other kinds of mutants of interest. The first
are antigenic variants such as those that occur frequently
Some deletion mutants have the unusual property of
with influenza viruses, which have an altered surface protein
and are therefore no longer inhibited by a person’s preexist-
being defective interfering particles. They are defective
ing antibody. The variant can thus cause disease, whereas the cause pneumonia.
because they cannot replicate unless the deleted function is
supplied by a “helper” virus. They also interfere with the
original strain cannot. Human immunodeficiency virus and
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hepatitis C virus also produce many antigenic variants.
growth of normal virus if they infect first and preempt the
These viruses have an “error-prone” polymerase that causes
required cellular functions. Defective interfering particles
the mutations. The second are drug-resistant mutants,
fere with the production of progeny virus, thereby limiting
which are insensitive to an antiviral drug because the target
of the drug, usually a viral enzyme, has been modified.
the spread of the virus to other cells.
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