TIM-family proteins also play role in Ebola and other viral infections

COLUMBIA, Mo. - A family of proteins that promotes virus entry into cells also has the ability to block the release of HIV and other viruses, University of Missouri researchers have found.

"This is a surprising finding that provides new insights into our understanding of not only HIV infection, but also that of Ebola and other viruses," said Shan-Lu Liu, M.D., Ph.D., associate professor in the MU School of Medicine's Department of Molecular Microbiology and Immunology.

The study was recently published in the Proceedings of the National Academy of Sciences. Liu, the corresponding author of the study, is also an investigator with the Christopher S. Bond Life Sciences Center at MU.

According to estimates from the Centers for Disease Control and Prevention, more than one million Americans are currently living with HIV infection, which can cause AIDS. AIDS, which stands for acquired immunodeficiency syndrome, is a condition characterized by progressive failure of the immune system. It is caused by the human immunodeficiency virus type 1 (HIV-1).

When HIV-1 or any virus infects a cell, it replicates and spreads to other cells. One type of cellular protein - T cell immunoglobulin and mucin domain, or TIM-1 - has previously been shown to promote entry of some highly pathogenic viruses into host cells. Now, the MU researchers have found that the same protein possesses a unique ability to block the release of HIV-1 and Ebola virus.

"This study shows that TIM proteins keep viral particles from being released by the infected cell and instead keep them tethered to the cell surface," said Gordon Freeman, Ph.D., an associate professor of medicine with Harvard Medical School's Dana-Farber Cancer Institute, who was not affiliated with the study. "This is true for several important enveloped viruses including HIV and Ebola.
We may be able to use this insight to slow the production of these viruses."

Under the supervision of Liu, Minghua Li, a graduate student in the MU Pathobiology Area Program, performed a series of experiments that revealed the protein's ability to inhibit HIV-1 release, resulting in diminished viral production and replication.

HIV-1 attacks cells that are vital to the body's immune system, such as T cells. These white blood cells play an important role in the body's response to infection, but HIV-1 disrupts the cells' ability to fight back against infection. When the virus enters a host cell, it infects the cell and replicates, producing viral particles that spread to and infect other cells. The researchers found that as the viral particles attempt to bud from, or leave, the infected cell, the TIM-family proteins located on the surface of the cell can attach to lipids on the surface of the viral particle.

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