Protein family 'tethers' HIV

Researchers at the University of Missouri School of Medicine (UMSM) have found that TIM-family proteins have the ability to block the release of HIV and other viruses such as Ebola.

A full account of the study has been published in Proceedings of the National Academy of Sciences.

According to UMSM associate professor Shan-Lu Liu, these “surprising findings” could provide new insights into our understanding of HIV, as well as a number of other viruses.

“This discovery furthers our ultimate goal of understanding the biology of TIM-family proteins

UMSM professor Shan-Lu Liu

When HIV 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, UMSM researchers said.

In this latest study, UMSM researchers have shown how TIM proteins have the ability to keep viral particles from being released by infected cells.

“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,” said Gordon Freeman, associate professor of medicine with Harvard Medical School’s Dana-Farber Cancer Institute.

In the example of HIV, the virus 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 disrupts the cells’ ability to fight back against infection, a UMSM statement said.

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, effectively tethering the virus to the cell, forcing the viral particles to accumulate on the surface of the host cell, rather than being released to infect other cells.

By using molecular, biochemical and electron microscopy techniques, the researchers were able to observe TIM and phosphatidylserine (PS) interactions in human cells.

The next step is for the researchers to study the biological significance of TIM-family proteins in animals and patients and to determine the fate of the infected cell once it accumulates a build-up of viral particles, UMSM said.

“We are not at the point to draw a conclusion as to whether this is a positive or a negative factor,” Liu said.

“However, this discovery furthers our ultimate goal of understanding the biology of TIM-family proteins and potentially developing applications for future antivirus therapies.”