Health News
Scavenger cells could be key to treating
HIV-related dementia
GAINESVILLE, Fla. - Bacteria-eating cells that generally fight infection may cause dementia in HIV patients, University of Florida and University of California at San Francisco researchers have found.
Macrophages, long-living white blood cells often considered the scavengers of the immune system, actually may damage a part of the brain where many memories are stored in their attempt to attack the virus there, according to findings reported in the Journal of Virology this month.
Researchers found that HIV-infected macrophages in the brain continuously travel to the temporal lobe, a part of the brain Alzheimer's disease often damages. Because the virus mutates nearly 100 times faster in the temporal lobe than other parts of the brain, attacking macrophages migrate there in a constant stream, causing harmful inflammation.
Nearly 15 percent of HIV patients develop dementia as their disease progresses. But understanding the routes macrophage cells take in the brain could help researchers find ways to block the migration and prevent HIV-associated dementia, said Marco Salemi, Ph.D, a UF assistant professor of pathology and immunology and an author of the study.
"In a way, it's not the virus that directly causes the dementia," Salemi said. "It's the fact that there is this continuous migration of infected macrophages to the temporal lobe. The virus mutates much faster there, the macrophages keep accumulating and keep creating this inflammation that leads to dementia."
Macrophages also may explain why current drugs cannot kill the virus that causes AIDS.
Researchers have known for years how HIV replicates in T cells, also part of the immune system. But most are just beginning to understand how the virus affects macrophages, said Michael S. McGrath, M.D., Ph.D, a UCSF professor of pathology and laboratory medicine who co-authored the study.
"It's likely the oldest (form of the) virus lives in a macrophage in the brain and most virus strains evolve from that," McGrath said. "Imagine having cells, already infected, that live as long as you do."
Current antiretroviral drugs block HIV from replicating in new T cells, but don't kill the virus in infected macrophages. And the drugs cannot stop the virus from evolving into new forms, McGrath said. Because the virus mutates faster than other cells in the body, it also can develop resistance to these drugs, Salemi said.
Even the HIV already in an infected person's brain is not one single virus, but rather populations of slightly different viruses that infect different parts of the brain, the findings show.
"We agree there are different strains that populate different regions of the brain," said Francisco Gonzalez-Scarano, M.D., chairman of the University of Pennsylvania neurology department. "We've done similar studies in monkeys."
To obtain their findings, the researchers studied different regions of the brain of a person who died with HIV-associated dementia using specimens from the AIDS and Cancer Specimen Resource at UCSF. They also used a new computer-based research tool to study the results. Dubbed phylodynamic analysis, this new method links traditional ways of studying the virus to give researchers a more comprehensive understanding, which Salemi says is crucial to analyzing the ever-changing disease.
"If we really want to understand what happens to a person infected with this disease, we need to develop new tools," he said. "We can put together all these different resources and describe how the virus changes over time and try to understand why this particular damage happens"
But these results are just a first step, Salemi said. The team is now analyzing brains from 10 people, some who died with HIV-associated dementia and others who did not.
The well-known cocktail of antiretroviral drugs prescribed to most HIV patients has cut the number of HIV-associated dementia cases reported each year, Gonzalez-Scarano said. However, this is because the drugs slow the progression of the disease, he said. Patients still have the same chance of developing dementia later, as the disease advances.
That's one of the reasons why the researchers say developing drugs that target macrophages as well as T cells is important. These drugs could provide better treatments for dementia and potentially lead to a way to "eradicate HIV-1 infection," the study states.
"You can't cure (HIV) with antiretroviral therapy (alone)," McGrath said.
Researchers from the University of California at Irvine, the University of Oxford and Gene Johnson Inc. also contributed to the study, which was funded by the National Science Foundation, the National Institutes of Health and the National Cancer Institute.
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UF scientist finds unexpected link between cat and human AIDS viruses
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GAINESVILLE, Fla. - A University of Florida researcher has discovered an unexpected link between the viruses that cause feline and human AIDS: Cats vaccinated with an experimental strain of the human AIDS virus appear to be at least as well-protected against the feline version of the disease as those immunized with the vaccine currently used by veterinarians.
The surprise finding may mean cats with feline immunodeficiency virus, also known as FIV or feline AIDS, could eventually be treated even more effectively using some form of the experimental human vaccine.Researcher Janet Yamamoto, a professor at UF's College of Veterinary Medicine, also theorizes that these emerging relationships between the two viruses could one day lead to a vaccine for human AIDS.
Results from Yamamoto's research can be previewed in today's (Sept. 8) online issue of the journal AIDS.
FIV is a natural infection of domestic cats that results in an immunodeficiency syndrome resembling HIV infection in humans. Since its discovery in 1987, FIV infection of cats has been used in vaccine studies as a small-animal model of human AIDS.
"We were the first to demonstrate that you can make an effective vaccine against a virus in the AIDS family of viruses," said Yamamoto, a co-discoverer of FIV.
Yamamoto holds the patent on the only approved vaccine available through veterinarians to protect cats against FIV. Her most recent studies have attempted to improve the efficacy of that vaccine by using strains of FIV found in cats in which the disease had not progressed for some reason over several years.
To determine the extent to which the human and feline AIDS viruses react to each other, and any implications that might exist for vaccine efficacy, Yamamoto began experimenting with long-term, nonprogressive strains of FIV that led to the current commercial vaccine. Now she is working on an HIV vaccine consisting of HIV virus from long-term, nonprogressing individuals.
"We purposely made vaccines with strains that weren't virile," Yamamoto said. "We found that whenever we tried using less virulent strains of virus, we were able to make a better vaccine."
Yamamoto's team was also surprised to discover that a core protein found in HIV also effectively protects cats against FIV.
"So what does this mean to human AIDS research? The viruses HIV and FIV are from the same viral family," Yamamoto said. "For that reason, the amino acids that make up the proteins in both viruses share some common regions. There appear to be regions of HIV, or variations of the core protein we used in our studies, that may provide protection in vaccine form against HIV."
Some compounds made from separate virus strains have been successfully used in vaccines against viruses from the same subfamily, such as smallpox in humans, which is made from cowpox virus, and human measles vaccines for canine distemper in puppies.
"Therefore, protective vaccines based on cross-reactive regions of AIDS viruses can provide broad immunity, and may be useful against viruses that are currently evolving in a new host, such as HIV infection of humans," Yamamoto said.
Alan L. Landay, a professor of immunology and microbiology and associate department chairman at Rush University Medical Center in Chicago called Yamamoto's findings "very exciting."
"This raises a potential whole new area for research in the field of vaccines that with the current approaches haven't yielded any success to date," said Landay, whose research team is working to develop novel immune strategies to treat HIV infection. "We need to explore all the potential options available to us for developing an HIV vaccine."
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