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."