Small Protein Plays a Big Role in the Impact of HIV on the Brain

A lack of the small protein interferon-β (IFNβ), which is involved in cell signaling and is integral to the body’s natural defense mechanism against viral infections, can compromise brain function in patients with HIV, according to a study published in the journal Brain Behavior and Immunity. 

NeuroHIV, which refers to the effects of HIV infection on the brain or central nervous system, is a collection of diseases, including neuropathy and dementia. NeuroHIV can also cause problems with memory and thinking, impeding the ability to lead a normal life.

Using a mouse model of neuroHIV, a research team assessed the impact of IFNβ on HIV infection. The researchers found that higher or lower than normal levels of IFNβ affect the brain in a sex-dependent fashion; some changes only occur in females, others only in males. The study found that when infection-induced IFNβ levels are high, the brain is protected. Conversely, if IFNβ production in response to infection is absent or too low, HIV can compromise brain function immediately in both females and males.

“Until now, it was not known that normal levels of IFNβ are required for normal memory function and that the absence of IFNβ changes the production of nerve cell components in a sex-dependent fashion,” said Marcus Kaul, PhD, a professor of biomedical sciences at the UC Riverside School of Medicine, via a press release.

“HIV and some other viruses have developed mechanisms to reduce or even prevent the production of more than normal levels of IFNβ,” said Hina Singh, an assistant project scientist in Dr. Kaul’s lab and the first author of the research paper. “We know little about the role of IFNβ in the human brain beyond that it can reduce inflammation. This is a major reason IFNβ is used to treat multiple sclerosis, an autoimmune disease that affects more than 2.8 million people worldwide. Currently, we have almost no information about how much IFNβ is present in the brains of [people living with HIV infection (PLWH)] and what it does there.”

Moving forward, the team plans to work on elucidating the findings of the neuroHIV model in PLWH. “For this, we will need to investigate tissues of PLWH who consented to donate them for research after death,” Dr. Kaul said. “Ultimately, we hope to develop IFNβ into a therapy for patients with neuroHIV.”