Feline Virus, Antiviral Drug Studied
to Learn Drug Resistance

Researchers at Ohio State will spend the next two years
testing their theories about just how an AIDS-like virus in
cats is able to resist the powerful medicines that are
thrown against it. It's one of the latest efforts at
understanding one of the leading problem areas in
medicine today - antimicrobial drug resistance.

When bacteria or viruses become resistant to drugs, they
become more difficult, or even impossible, to treat. The
project, funded by the National Institute on Drug Abuse,
could reveal how some viral infections become able to
withstand antiviral medications and even thrive in the
presence of some drugs. If successful, the research might
pave the way to smarter, more effective treatments for a
host of pathogens that have learned to resist most
therapeutic efforts.

The project grew from important discoveries made five
years ago as part of a controversial research program
investigating the impact of methamphetamine on feline
immunodeficiency virus (FIV) – one of only three animal
viruses that can be used to mimic HIV (human
immunodeficiency virus) infections in humans.

Surprisingly, that project showed that the virus was able
reproduce itself 15 times faster when methamphetamine
was present. The work also showed that FIV mutated
rapidly to adapt to grow in astrocytes, the dominant cell
type within the brain, and that this phenomenon was
accelerated by exposure to methamphetamine. If the virus
becomes drug-resistant as it routinely mutates into this
new form, would that drug resistance occur earlier if
methamphetamine were present ?  After an initial phase
five years ago that used cats as the animal model for the
study, research shifted to more refined work with cell
cultures of astrocytes grown in the laboratory, focusing on
the changes taking place in individual cells. The same
mutated form of FIV would probably be present in the
brains of infected cats.

Researchers turned to tissue stored from another decade-
old unrelated project that looked at how the virus
suppressed the animals' immune systems. They found that
the same virus mutations in the cultured cell experiments
were present in that brain tissue but only after long-term
infection. The new research grant will use tissue culture
methods to look specifically at how the presence of
methamphetamine may increase the virus' ability to resist
antiviral drugs, in this case, a powerful AIDS drug called
azidothymidine, or AZT.

The researchers will treat FIV-infected cell cultures with low
concentrations of AZT, forcing it to develop a resistance to
the drug, repeating the procedure in the presence of
methamphetamine. They know how long it normally takes
the mutation to appear in the virus and predict that it will
appear earlier in cells exposed to both AZT and
methamphetamine. The first year of the project is focused
on continued in vitro studies using both FIV and cat cell
lines as well as parallel experiments with HIV in human cell
lines. If the results are promising, the researchers will test
the drugs' interactions with the virus in a small study using
two dozen cats in the second year.

                                                                                                   November 2007
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