Exposure to methamphetamine can enhance up to 15 times the expression of feline immunodeficiency virus (FIV) in tissue-cultured brain cells from cats, according to research performed at The Ohio State University (OSU).
Exposure to methamphetamine can enhance up to 15 times the expression of feline immunodeficiency virus (FIV) in tissue-cultured brain cells from cats, according to research performed at The Ohio State University (OSU).
The finding may provide insight into human HIV, of which FIV is a surrogate,researchers say.
Methamphetamine, an abused substance among drug users, has been linkedwith a more aggressive form of AIDS in humans, according to Dr. Larry Mathes,Ph.D. of OSU's College of Veterinary Medicine, and one of the lead researcherson the in vitro study.
"The importance is that if we knew why methamphetamine seemed tohave a more aggressive form of disease then we may have a better way totreat AIDS in humans," says Mathes.
By evaluating animal models, which have simimilar pathogenesis, Mathessays it's possible to determine the effects of methamphetamine. "It'sa remarkable find that even in tissue culture we're able to show that methamphetamineseems to increase the rate of virus expression," he adds.
Controversial side
Because the study involved tissue culture of animals, little controversysurfaced. But the study is being funded by the same grant that includesstudies that do involve use of methamphetamine in cats, which has stirredopposition with groups such as People for the Ethical Treatment of Animalsand other animal rights activists.
"Controversial is not how I would define the study," Mathessays. "It means there is a question. The question is only in the mindsof individuals who under no circumstances would feel it's justified to useanimals. I respect that view. I don't agree with it. Certain circumstanceswarrant it. Unfortunately it's not something one can debate, because forthose people who really believe that no animals should be used in research,there's no circumstance where I could convince them otherwise.
"The university has a position, of course, that they support appropriateanimal research. We have stringent guidelines. All protocols have to beapproved. This is not helter-skelter, it's monitored at all levels."
The next experiment is to get human astrocyte tissue cultures and humanlymphocytes and do the same type of experiment and see if there is enhancedexpression of virus there as well.
"Ultimately it may lead to a better understanding of how to preventthe neurological part of the disease. We have to remember that while wehave a cocktail of drugs that is pretty good temporarily for suppressingvirus and allows people infected with HIV to live a lot longer, the questionof neurologic outcome is still up in the air," says Mathes.
Bonus finding
An unexpected discovery was the route of infection. In the brain of ahuman or cat, a number of blood-brain barriers fight to keep toxins andinfectious agents out.
There is a scheme by which white blood cells, or lymphocytes, can crossthe blood-brain barrier in looking for infectious agents and then can moveback into the blood, reports Mathes. Occasionally lymphocytes, which canbe infected with FIV or HIV, will cross the barrier.
"What Dr. Podell (lead researcher) and the laboratory researchersdiscovered was that if you mix in tissue-culture-infected lymphocytes withastrocytes (brain cells), the virus does transmit to the astrocytes ingreat number," he says. If it occurred at a rate of one for example,when methamphetamine was added, the rate went up to 10.
"Methamphetamine is enhancing this transmission of virus from lymphocytesto astrocytes," Mathes says, adding that unfortunately these are onlycell tissues, not animals.
The discoveries then were cell-to-cell transmission from lymphocytesto astrocytes, that methamphetamine increased the rate of infection, andone other unplanned outcome.
"If you were able to grow those infected astrocytes in tissue culture,as we did, they produced a mutated virus an altered form of virusthat could infect other astrocytes without the lymphocytes," Mathessays. This process, too, is enhanced by methamphetamine.