Sugar-binding protein may play a role in HIV infection

June 14, 2011

Specific types of "helper" T cells that are crucial to maintaining functioning immune systems contain an enzyme called PDI (protein disulfide isomerase).

This enzyme affects how proteins fold into specific shapes, which in turn influences how the behave. PDI also plays a role in HIV infection by helping to change the shape of the surface of the virus, enabling the virus to interact optimally with receptors on the T cells, such as the CD4 molecule.

Though it is known that PDI inhibitors can prevent HIV infection, just how this happens has remained a mystery. And though it has been known that PDI, which normally lives inside the cell, can become entrapped on the cell's surface, it has not been understood how this happens.

Now, in a new study, UCLA researchers report that a sugar-binding protein called galectin-9 traps PDI on T-cells' surface, making them more susceptible to .

The findings could lead researchers to a potential new target for anti-HIV therapeutics, such as therapies to inhibit PDI or galectin-9.

Explore further: Research sheds new light on how blood clots form

More information: Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry, PNAS, Published online before print June 13, 2011, doi: 10.1073/pnas.1017954108

Interaction of cell surface glycoproteins with endogenous lectins on the cell surface regulates formation and maintenance of plasma membrane domains, clusters signaling complexes, and controls the residency time of glycoproteins on the plasma membrane. Galectin-9 is a soluble, secreted lectin that binds to glycoprotein receptors to form galectin–glycoprotein lattices on the cell surface. Whereas galectin-9 binding to specific glycoprotein receptors induces death of CD4 Th1 cells, CD4 Th2 cells are resistant to galectin-9 death due to alternative glycosylation. On Th2 cells, galectin-9 binds cell surface protein disulfide isomerase (PDI), increasing retention of PDI on the cell surface and altering the redox status at the plasma membrane. Cell surface PDI regulates integrin function on platelets and also enhances susceptibility of T cells to infection with HIV. We find that galectin-9 binding to PDI on Th2 cells results in increased cell migration through extracellular matrix via β3 integrins, identifying a unique mechanism to regulate T-cell migration. In addition, galectin-9 binding to PDI on T cells potentiates infection with HIV. We identify a mechanism for regulating cell surface redox status via a galectin–glycoprotein lattice, to regulate distinct T-cell functions.

Related Stories

Research sheds new light on how blood clots form

June 13, 2011

Scripps Research Institute scientists have discovered new elements of the blood clot-formation process. The findings could lead to better drugs for preventing heart attacks and other clot-related conditions.

Recommended for you

Videos reveal how HIV spreads in real time

October 2, 2015

How retroviruses like HIV spread in their hosts had been unknown—until a Yale team devised a way to watch it actually happen in a living organism. The elaborate and sometimes surprising steps the virus takes to reach and ...

Researchers find proteins that shut down HIV-1

September 30, 2015

A pair of studies by researchers at the University of Massachusetts Medical School, the University of Trento in Italy, and the University of Geneva in Switzerland, point to a promising new anti-retroviral strategy for combating ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.