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 mimick 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.
That observation led to an epiphany of sorts,
explained Lawrence Mathes, professor of veterinary
biosciences and associate dean for research and
graduate studies in the College of Veterinary Medicine
and principal investigator on the project.
If the virus becomes drug-resistant as it
routinely mutates into this new form, would that drug
resistance occur earlier if methamphetamine were
present? he asked.
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. Mathes
reasoned that the same mutated form of FIV would
probably be present in the brains of infected cats.
He and his colleagues turned to tissue stored from
another decade-old unrelated project that looked at
how the virus suppressed the animals' immune systems.
We went back to those tissues and, in fact, found
that the same virus mutations we saw in the cultured
cell experiments were present in that brain tissue but
only after long-term infection, he said.
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 anitiviral drugs, in this case, a powerful AIDS
drug called azidothymidine, or AZT.
We know a lot about AZT, how it works and what
mutations it causes in the virus, he said. 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.
We know how long it normally takes the mutation to
appear in the virus. We predict that it will appear
earlier in cells exposed to both AZT and
methamphetamine, he said.
Mathes said that 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.
