Page 381 - Review of Medical Microbiology and Immunology ( PDFDrive )

mebooksfree.com
mebooksfree.com
mebooksfree.com

mebooksfree.com
mebooksfree.com
mebooksfree.com
mebooksfree.com
mebooksfree.com
mebooksfree.com mebooksfree.com mebooksfree.com polymerase II. At each end is a sequence called an LTR mebooksfree.com
PART IV Clinical Virology
370
3
contain SV40 DNA, but the relationship of that DNA to
malignant transformation is uncertain.
that is composed of several regions, one of which, near the
5′ end, is the binding site for the primer tRNA.
After infection of the cell by a retrovirus, the following
ANIMAL TUMOR VIRUSES
events occur: Using the genome RNA as the template, the
1. RNA Tumor Viruses
synthesizes double-stranded proviral DNA. The DNA then
RNA tumor viruses have been isolated from a large number
integrates into cellular DNA. Integration of the proviral
of species, namely, snakes, birds, and mammals, including reverse transcriptase (RNA-dependent DNA polymerase)
DNA is an obligatory step, but there is no specific site of
nonhuman primates. The important RNA tumor viruses are
mebooksfree.com
integration. Insertion of the viral LTR can enhance the
mebooksfree.com mebooksfree.com mebooksfree.com This explains how retroviruses without viral oncogenes can mebooksfree.com
mebooksfree.com
listed in Table 43–7. They are important because of their
transcription of adjacent host cell genes. If this host gene is
ubiquity, their ability to cause tumors in the host of origin,
a cellular oncogene, malignant transformation may result.
their small number of genes, and the relationship of their
genes to cellular oncogenes (see page 363).
cause transformation.
These viruses belo ng to the retrovirus family (the pre-
fix retro means reverse), so named because a reverse tran-
2. DNA Tumor Viruses
scriptase is located in the virion. This enzyme transcribes
Papovaviruses
the genome RNA into double-stranded proviral DNA and
is essential to their replication. The viral genome consists
of two identical molecules of positive-strand RNA. Each
polyomavirus and SV40 virus. Polyomavirus (poly means
6
molecule has a molecular weight of approximately 2 × 10
many; oma means tumor) causes a wide variety of histo-
(these are the only viruses that are diploid [i.e., have two The two best-characterized oncogenic papovaviruses are
logically different tumors when inoculated into newborn
copies of their genome in the virion]). The two molecules
mebooksfree.com mebooksfree.com mebooksfree.com biologic features (e.g., double-stranded, circular, super- mebooksfree.com
mebooksfree.com
mebooksfree.com
rodents. Its natural host is the mouse. SV40 virus, which
are hydrogen-bonded together by complementary bases
was isolated from normal rhesus monkey kidney cells,
located near the 5′ end of both RNA molecules. Also
causes sarcomas in newborn hamsters.
bound near the 5′ end of each RNA is a transfer RNA
Polyomavirus and SV40 virus share many chemical and
2
(tRNA) that serves as the primer for the transcription of
the RNA into DNA.
6
coiled DNA of molecular weight 3 × 10 and a 45-nm ico-
The icosahedral capsid is surrounded by an envelope
sahedral nucleocapsid). However, the sequence of their
with glycoprotein spikes. Some internal capsid proteins are
DNA and the antigenicity of their proteins are quite dis-
group-specific antigens, which are common to retroviruses
tinct. Both undergo a lytic (permissive) cycle in the cells of
within a species. There are three important morphologic
their natural hosts, with the production of progeny virus.
types of retroviruses, labeled B, C, and D, depending pri-
marily on the location of the capsid or core. Most of the
cies, the nonpermissive cycle ensues, no virus is produced,
retroviruses are C-type particles, but mouse mammary
and the cell is malignantly transformed.
tumor virus is a B-type particle, and HIV, the cause of However, when they infect the cells of a heterologous spe-
In the transformed cell, the viral DNA integrates into
mebooksfree.com
mebooksfree.com mebooksfree.com mebooksfree.com are required for induction and maintenance of the trans- mebooksfree.com
mebooksfree.com
AIDS, is a D-type particle.
the cell DNA, and only early proteins are synthesized. Some
The gene sequence of the RNA of a typical avian sar-
of these proteins (e.g., the T antigens described on page 353)
coma virus is gag, pol, env, and src. The nontransforming
retroviruses have three genes; they are missing src. The gag
formed state.
region codes for the group-specific antigens, the pol gene
JC virus, a human papovavirus, is the cause of progres-
codes for the reverse transcriptase, the env gene codes for
sive multifocal leukoencephalopathy (see Chapter 44). It
the two envelope spike proteins, and the src gene codes for
also causes brain tumors in monkeys and hamsters. There
the protein kinase. There is evidence that the kinase phos-
is no evidence that it causes human cancer.
phorylates signal tranduction factors that activate synthesis
of cyclins that drive the cell into S phase and subsequent
mitosis.
The sequences at the 5′ and 3′ ends function in the inte-
Some human adenoviruses, especially serotypes 12, 18, and 31,
gration of the proviral DNA and in the transcription of Adenoviruses
induce sarcomas in newborn hamsters and transform
mebooksfree.com mebooksfree.com mebooksfree.com 3 the virus. mebooksfree.com mebooksfree.com mebooksfree.com
mRNA from the integrated proviral DNA by host cell RNA
rodent cells in culture. There is no evidence that these
2
The purpose of the primer tRNA is to act as the point of attachment for
The length of the sequence varies from 250 to 1200 bases, depending on
the first deoxynucleotide at the start of DNA synthesis. The primers are
normal-cell tRNAs that are characteristic for each retrovirus.
mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com