FEB 12, 2019 4:27 PM PST

Measuring Up HIV

WRITTEN BY: Nicholas Breehl

George Mason University's Yuntao Wu is the lead scientist on a research team that has identified a measurable indicator that could prove instrumental in the fight against HIV.

The research focuses on cofilin, an essential protein that regulates cells to mobilize and fight against infection.

In an HIV-infected patient, cofilin dysfunction is a critical factor in helper T cell defects, according to the research recently published in the journal Science Advances. Helper T cells augment the body's immune response by recognizing the presence of a foreign antigen and then helping the immune system mount a response.

"When you have an infection, you need to mobilize the T cells," said Wu, a College of Science professor of Molecular and Microbiology within Mason's School of Systems Biology and National Center for Biodefense and Infectious Diseases. "In HIV infection, there is a profound depletion of helper T cells in lymphoid tissues, such as those in the gut."

Antiretroviral therapy has significantly increased the lifespan of HIV-infected people, although it offers neither a cure nor a full restoration of the body's immune system, he said. The natural course of the HIV infection leads to multiple immune defects, including the impairment of T cell migration, according to the research team.

Wu and his team found that patients with HIV have "significantly lower" levels of cofilin phosphorylation -- which provides control of cofilin's activity with the addition of a phosphate -- than healthy patients. Cofilin is a critical protein that helps cells generate the driving force for migration. Proper cofilin phosphorylation is needed for cells to move in and out of tissues.

Their findings suggest that a lasting immune control to HIV isn't likely to come from antiretroviral therapy alone because it is not sufficient to repair the cofilin damage caused by HIV and to restore normal T cell migration in and out of tissues.

But the researchers found that by stimulating the T cells with additional therapeutics, such as the ?4?7 integrin antibody, they could modulate the levels of cofilin activity needed to restore T cell mobility. The remedy has shown lasting effects in immune control of simian immunodeficiency virus (SIV), the animal form of the AIDS virus, in a monkey trial, but it has not shown the same results in HIV-infected human patients.

"Now we have a marker, and at least one target that we can focus on to discover new therapies to repair the immune damages for a functional cure," Wu said.

Sources: Science Daily, Science Advances, YouTube

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