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July 6, 2006 -- In the month that marks the 25th anniversary
of the first reported cases of AIDS in the United States,
University of Virginia Health
System researchers have published
pioneering work describing a model system for long-term
infection with a virus known as the Kaposi’s sarcoma-associated
herpesvirus (KSHV), which causes Kaposi’s sarcoma
(KS) — the most common AIDS-related cancer worldwide
and the original harbinger of the AIDS epidemic in this
country.
This work, led by Dr. Dean Kedes, associate professor of
Internal Medicine and Microbiology, successfully recapitulated
viral replication events within a mouse model system mimicking
those observed in human patients, including infection of
white blood cells with the expression of non-structural
proteins promoting viral persistence, followed by increasing
expression of structural proteins required for assembly
of whole virus particles and spread of the infection. Addition
of human immune cells to the model resulted in the production
of KSHV-specific antibodies found in the serum of mice
indistinguishable from those found in the serum of human
patients infected with the virus and suffering from KS,
according to the study published in the Journal of Clinical
Investigation (www.jci.org).
The researchers also found that the antiviral agent ganciclovir
successfully prevented the production of structural proteins
by the virus, although it did not prevent initial infection
of white blood cells. After the drug was stopped, viral
replication resumed, supporting the contention that novel
therapies are needed to treat and prevent this infection.
“I am very excited about these results and the new possibilities
that this model opens to develop novel ways of preventing
and treating the diseases caused by this human virus,” said
Dr. Kedes, a member of the University’s Myles H.
Thaler Center for AIDS and Retrovirus Research. The work
was a collaborative effort between Dr. Kedes’s laboratory,
where Dr. Christopher Parsons spearheaded the work, and
the laboratory of Dr. David Camerini, a former member of
UVa’s Department of Microbiology and now at the
University of California, Irvine. The researchers will
now use this
model to study mechanisms by which KSHV enters host cells
and manipulates the cellular machinery to cause tumors.
Perhaps equally important, the model will allow for more
effective preclinical testing of drugs designed to treat
KSHV infection and KS.
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