Page 380 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 43 Tumor Viruses
lymphomas in marmoset monkeys. It is also associated
Chapter 41.)
with nasopharyngeal carcinoma, a tumor that occurs pri-
marily in China, and with thymic carcinoma and B-cell
Merkel Cell Polyomavirus
lymphoma in the United States. However, cells from
Burkitt’s lymphoma patients in the United States show no
Merkel cell polyomavirus (MCPV) causes a carcinoma of
evidence of EBV infection. (Additional information regard-
ing EBV can be found in Chapter 37.)
for pressure and touch.) The carcinoma occurs most often
Cells isolated from East African individuals with
on skin exposed to the sun such as the face and neck.
Burkitt’s lymphoma contain EBV DNA and EBV nuclear Merkel cells in the skin. (Merkel cells are neuroreceptors
Immunosuppressed individuals and the elderly are predis-
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antigen. Only a small fraction of the many copies of EBV
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posed to this cancer.
DNA is integrated; most viral DNA is in the form of closed
Members of the polyomavirus family are small, nonen-
circles in the cytoplasm.
The difficulty in proving that EBV is a human tumor
cancer in animals (see later section on animal tumor
virus is that infection by the virus is widespread but the
viruses). Infection with MCPV is common as indicated by
tumor is rare. The current hypothesis is that EBV infection
the presence of antibody to the virus in many healthy blood
induces B cells to proliferate, thus increasing the likelihood
donors. The mode of transmission is uncertain.
that a second event (e.g., activation of a cellular oncogene)
In carcinoma cells, the DNA of MCPV is integrated into
will occur. In Burkitt’s lymphoma cells, a cellular oncogene,
cell DNA. The gene for the large T antigen is mutated so the
c-myc, which is normally located on chromosome 8, is
translocated to chromosome 14 at the site of immuno-
synthesized. The T antigen causes the cell to become malig-
globulin heavy chain genes. This translocation brings the
nant by inhibiting tumor suppressor proteins such as p53
c-myc gene in juxtaposition to an active promoter, and virus cannot replicate but the T antigen continues to be
and RB. Because MCPV does not replicate in the carci-
large amounts of c-myc RNA are synthesized. It is known
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noma cells, patients are not infectious to others.
that the c-myc oncogene encodes a transcription factor, but
Diagnosis is made by pathologic analysis of surgical
the role of this factor in oncogenesis is uncertain.
specimens. There is no virus-based laboratory test clini-
Human Herpesvirus 8
able. Prevention involves reducing sun exposure, use of
sunscreen, and frequent skin examinations to detect the
Human herpesvirus 8 (HHV-8), also known as Kaposi’s
cancer before it metastasizes.
sarcoma–associated herpesvirus (KSHV), causes Kaposi’s
sarcoma (KS). KS is a malignancy of vascular endothelial
cells that contains many spindle-shaped cells and erythro-
VACCINES AGAINST CANCER
cytes. It is the most common cancer in patients with
acquired immunodeficiency syndrome (AIDS). KSHV is
transmitted both sexually and by saliva. A protein encoded
the HBV vaccine and the HPV vaccine. The widespread use
by KSHV called latency-associated nuclear antigen (LANA) There are two vaccines designed to prevent human cancer:
of the HBV vaccine in Asia has significantly reduced the
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inactivates RB and p53 tumor suppressor proteins, which
incidence of hepatocellular carcinoma. The vaccine against
causes malignant transformation of the endothelial cells.
HPV, the cause of carcinoma of the cervix, was approved
(Additional information regarding HHV-8 can be found in
for use in the United States in 2006.
Chapter 37.)
Hepatitis B Virus
CAUSE CANCER IN HUMANS?
HBV infection is significantly more common in patients
with primary hepatocellular carcinoma (hepatoma) than
There is no evidence that animal tumor viruses cause
tumors in humans. In fact, the only available information
in control subjects. This relationship is striking in areas of
Africa and Asia, where the incidence of both HBV infec-
tion and hepatoma is high. Chronic HBV infection com-
inoculated with poliovirus vaccine contaminated with
SV40 virus have no greater incidence of cancers than do
monly causes cirrhosis of the liver; these two events are the
main predisposing factors to hepatoma. Part of the HBV suggests that they do not, because (1) people who were
uninoculated controls, (2) soldiers inoculated with yellow
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genome is integrated into cellular DNA in malignant cells.
fever vaccine contaminated with avian leukemia virus do
However, no HBV gene has been definitely implicated in
not have a high incidence of tumors, and (3) members of
oncogenesis. The integration of HBV DNA may cause
families whose cats have died of leukemia caused by feline
insertional mutagenesis, resulting in the activation of a cel-
lular oncogene. In addition, the HBx protein may play a
kemia over control families. Note, however, that some
role because it inhibits the p53 tumor suppressor protein.
human tumor cells, namely, non-Hodgkin’s lymphoma,
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