Page 310 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 37 DNA Enveloped Viruses
299
an immunoglobulin gene promoter. This enhances synthe-
sis of the c-myc protein, a potent oncoprotein. The c-myc
protein is a transcriptional regulator that enhances the
synthesis of kinases that activate the cell cycle.

HUMAN HERPESVIRUS 8 (KAPOSI’S
SARCOMA–ASSOCIATED
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HERPESVIRUS)
In 1994, it was reported that a new herpesvirus, now
known as human herpesvirus 8 (HHV-8), or Kaposi’s sar-
coma–associated herpesvirus (KSHV), causes Kaposi’s
sarcoma (KS), the most common cancer in patients with
AIDS. The idea that a virus other than HIV is the cause of
KS arose from epidemiologic data showing that KS was
common in patients who acquired HIV sexually but rare
in patients who acquired HIV via blood transfusion. A
second virus transmitted sexually appeared likely to be
the cause.
The initial evidence that HHV-8 was involved was the
finding that most KS cells taken from AIDS patients con-
mebooksfree.com mebooksfree.com mebooksfree.com FIGURE 37–10 Kaposi’s sarcoma—note several dark purple mebooksfree.com
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tain the DNA of this virus, but tissues taken from AIDS
patients without KS had very little viral DNA. The DNA of
this virus was also found in KS cells that arose in non–HIV-
infected patients. On DNA analysis, HHV-8 resembles the
lymphotropic herpesviruses (e.g., EBV and herpesvirus
saimiri) more than it does the neurotropic herpesviruses,
such as HSV and VZV.
lesions on the foot caused by human herpesvirus 8 (Kaposi’s
Additional support was provided by serologic studies
sarcoma–associated virus). (Source: Public Health Image Library, Centers for
showing that most HIV-infected patients with KS had anti-
Disease Control and Prevention.)
bodies to HHV-8, whereas considerably fewer HIV-infected
patients without KS had antibodies to the virus, and very
few patients with other sexually transmitted diseases, but
who were not HIV-infected, had these antibodies. The cur- nodular, and often appear at multiple sites such as the skin,
oral cavity, and soles (but not the palms) (Figure 37–10).
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rent estimate of HHV-8 infection in the general population
Internally, lesions occur commonly in the gastrointestinal
ranges from about 3% in the United States and England to
tract and the lungs. The extravasated red cells give the
about 50% in East Africa.
lesions their purplish color. HHV-8 also infects B cells,
HHV-8 causes malignant transformation by a mecha-
nism similar to that of other DNA viruses (e.g., human
phoma called primary effusion lymphoma.
papillomavirus), namely, inactivation of a tumor suppres-
Laboratory diagnosis of KS is often made by biopsy of
sor gene. A protein encoded by HHV-8 called latency-
the skin lesions. HHV-8 DNA and RNA are present in most
associated nuclear antigen (LANA) inactivates RB and p53
spindle cells, but that analysis is not usually done. Virus is
tumor suppressor proteins, which causes malignant trans-
not grown in culture.
formation of endothelial cells.
The type of treatment depends on the site and number
Transmission of HHV-8 occurs primarily via sex and by
saliva, but it is also transmitted in transplanted organs such
or immunomodulatory drugs, such as alpha interferon can
as kidneys and appears to be the cause of transplantation- of the lesions. Surgical excision, radiation, chemotherapy,
be used. In early HIV-associated KS, highly active antiret-
associated KS. The DNA of HHV-8 is found in the cells of
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roviral drugs (HAART) can be effective treatment. Note
transplantation-associated KS but not in the cells of other
that anti-herpesvirus drugs, such as acyclovir, foscarnet,
transplantation-associated cancers.
and cidofovir are not effective.
KS in AIDS patients is a malignancy of vascular endo-
HAART also can prevent KS as evidenced by a decreased
thelial cells that contains many spindle-shaped cells and
erythrocytes. The lesions are reddish to dark purple, flat to
HAART. There is no vaccine against HHV-8.
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