Over 35 million people worldwide are currently infected by HIV. Antiviral therapies can keep the virus from multiplying. However, no drug can cure infection so far, because various cell types continue to carry the virus in a latent, i.e. quiescent, state. Scientists of Helmholtz Zentrum Muenchen have now established a model for latent HIV infection of brain cells. The researchers used this model to identify various compounds that affect latency of the virus in the brain. This study was published in the journal AIDS.
“Chronic infection is caused by long-lived cells with resting viral genomes that are activated by different factors,” explained Prof. Dr. Ruth Brack-Werner of the Institute of Virology. “These so-called latently infected cells occur in the blood and in the brain, among others. HIV latency in the brain is particularly difficult to investigate,” she added. Her research group is studying HIV persistence in a very important type of brain cells called astrocytes. The human brain contains billions of them. The many functions of astrocytes include protecting the brain from injury and harmful agents and providing essential support for nerve cells. Mature astrocytes can have a very long lifespan and may exist for years.
Recent studies identified HIV genomes in up to 19% of astrocytes in brain tissues from deceased HIV-1 infected individuals. So far, no experimental model has existed to study HIV latency in these cells. “With our model system, we can simulate latent HIV infection in astrocytes,” said Dr. Martha Schneider, first author of the study. The researchers showed that various substances, including the cytokine TNF-alpha, can reactivate the inactive virus. Conversely, it was also possible to inhibit the reactivation of the virus by treating the cells with certain compounds. “These results identify drug candidates that may prevent activation of latent viruses in astrocytes”, Schneider concluded.
In the future, the scientists plan to use this system to study the effect of these and other compounds that may prevent the activation of HIV-1 in the brain. As study director Brack-Werner explained: “Several viral proteins are toxic to neurons and may cause immune damage in the brain. Since only limited replacement of astrocytes occurs in the brain, loss of these cells may cause serious damage. Thus silencing the virus in brain cells is an important goal.” In addition, the researchers plan to test the effect of approved drugs and thus to improve the clinical care of HIV-1 patients in the future.
Original Publication: Schneider, M. et al. (2015). A new model for post-integration latency in macroglial cells to study HIV-1 reservoirs of the brain, AIDS, DOI:10.1097/QAD.0000000000000691
As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.
The Institute of Virology (VIRO) investigates viruses that chronically infect humans and can cause life-threatening diseases. The research activities of the institute focus mainly on the HI virus which causes AIDS, on endogenous retroviruses, which are integrated into our germline, and hepatitis B and C viruses, which cause liver cirrhosis and hepatocellular carcinoma. Molecular studies identify new diagnostic and therapeutic concepts to prevent and treat these viral diseases or to prevent the formation of virus-induced tumors.
Scientific contact at Helmholtz Zentrum Muenchen: Prof. Dr. Ruth Brack-Werner, Helmholtz Zentrum Muenchen - German Research Center for Environmental Health (GmbH), Institut fuer Virologie, Ingolstaedter Landstr.
Dr. Ruth Brack-Werner
Helmholtz Zentrum München - German Research Center for Environmental Health