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The HIV virus can take refuge in the brain during treatment and reappear once these treatments are stopped, a new study in mice and human tissue suggests.
By understanding the way HIV is able to hide away while antiretroviral therapies are being administered — only to later infect other organs in the body once treatment is stopped — scientists can add to a growing wealth of knowledge that could one day lead to a widely available cure for the virus.
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Fighting the 'worldwide HIV epidemic'
Did you know that, according to some scientists, COVID-19 isn't the only pandemic we are currently living through today? Though the World Health Organization (WHO) classes it as a 'worldwide epidemic', some consider HIV a pandemic.
Today, despite the fact that cases have been reduced by 40% since its peak in 1997, thanks to antiretroviral treatments, there are approximately 37 million people living with HIV.
Untreated HIV, the virus that causes AIDS, cripples the immune system, leaving the body vulnerable to life-threatening illness. Modern treatments significantly lower concentrations of the virus in the body to the point that the pathogen can become undetectable. However, this treatment must be taken daily: if treatment is stopped, it is possible for the virus to reemerge from hidden sanctuaries in our bodies.
The new study, published June 11 in the journal PLOS Pathogens, suggests that one of the locations where the virus is able to hide out is in brain cells called astrocytes. These constitute roughly 60% of the total cells in the human brain, and in an infected person, the study estimates that between 1% and 3% of these cells could harbor HIV.
"Even 1% could be significant as a reservoir, as a sanctuary site, for the virus," study author Lena Al-Harthi, a professor and chair in the Department of Microbial Pathogens and Immunity at Rush University Medical Center in Chicago, told LiveScience. "If we're going to try to find an HIV cure, you can't neglect the role of the brain as a reservoir."
Examining mouse models and human brain tissue
While astrocytes were identified as cells affected by the HIV virus years ago, no study had identified whether the cells could somehow release HIV to organs beyond the brain.
The team of scientists drew their findings from a mouse model of HIV injected with human cells, as well as examinations of postmortem human brain tissue.
For the mouse models, Al-Harthi and her team developed two new models to tackle this important question.
The scientists injected human fetal astrocytes into the brains of lab mice — one set of newborn mice and one set of adult mice. They found that, in both sets of mice, the infected astrocytes passed on the virus to CD4 cells — a type of immune cell that is specifically targeted by the HIV virus.
In order to confirm aspects of their mouse experiments, the authors examined the donated brain of four individuals who had successfully suppressed the virus using retroviral drugs at the time of their death.
The team found that a small percentage of astrocytes contained HIV genetic material in their nuclei, indicating that the cells had been infected by the virus.
Many questions still remain about the way that astrocytes are able to store HIV before reinfecting other organs — more tests are needed. In order to eventually find a successful cure for HIV that can be widely used, scientists will need to determine the exact route HIV takes out of the brain in order to infect other organs.
This way, they can aim to develop a special treatment that targets the brain and stops the virus from spreading again once it has been suppressed by retroviral treatments.