Sugar-binding protein may play a role in HIV infection

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.

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

Abstract
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

Scientists find another key to HIV success

date Mar 22, 2006

Weill Cornell Medical College scientists say they've determined a protein produced by HIV infected cells prevents immune B cells from producing antibodies.

How HIV hides itself

date Apr 01, 2008

Researchers have discovered how Human Immunodeficiency Virus (HIV), which causes AIDS, can hide itself in our cells and dodge the attention of our normal defences, scientists heard today at the Society for General Microbiology’s ...

How HIV vaccine might have increased odds of infection

date Nov 03, 2008

In September 2007, a phase II HIV-1 vaccine trial was abruptly halted when researchers found that the vaccine may have promoted, rather than prevented, HIV infection. A new study by a team of researchers at the Montpellier ...

Research sheds new light on how blood clots form

date Jun 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

Indiana HIV outbreak, hepatitis C epidemic sparks US alert

date Apr 24, 2015

Federal health officials helping to contain an HIV outbreak in Indiana state issued an alert to health departments across the U.S. on Friday, urging them to take steps to identify and track HIV and hepatitis C cases in an ...

Why are HIV survival rates lower in the Deep South than the rest of the US?

date Apr 22, 2015

The Deep South region has become the epicenter of the US HIV epidemic. Despite having only 28% of the total US population, nine states in the Deep South account for nearly 40% of national HIV diagnoses. This region has the highest HIV diagnosis rates and the highest number of people living with HIV of any ...

A bad buzz: Men with HIV need fewer drinks to feel effects

date Apr 20, 2015

Researchers at Yale and the VA Pittsburgh Healthcare System compared the number of drinks that men with HIV infection, versus those without it, needed to get a buzz. They found that HIV-infected men were more sensitive to ...

Research informs HIV treatment policy for inmates

date Apr 16, 2015

A national, five-year study of care for inmates with HIV brought strangers together, produced policy change in the Delaware Department of Corrections and documented the importance of good communication and ...

User comments

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.