Protein key to restoring `exhausted` HIV-fighting immune cells identified
Washington: Researchers have identified a protein that causes loss of function in immune cells combating HIV.
The scientists claimed that the protein, Sprouty-2, is a promising target for future HIV drug development, since disabling it could help restore the cells' ability to combat the virus that causes AIDS.
Jonathan Schneck, who led the study, said that a large part of the reason we lose wars against viruses that cause chronic infection is that immune cells called T cells get turned off.
To investigate the source of exhaustion, the Johns Hopkins team first sought a way to recreate that phenomenon in the laboratory.
Yen-Ling Chiu, graduate student in Schneck's laboratory, was able to simulate the effects of long-term chronic infection by growing influenza-fighting T cells and dosing them with large amounts of antigen, a type of molecule that signals immune cells to attack.
Chiu next looked for differences in proteins made in the dysfunctional cells compared to those in fresh T cells.
He said that many of the proteins whose quantities were different between the two groups of cells were involved in a biochemical chain of events called the MAPK/ERK pathway, which controls a variety of important processes.
One of the protein s that was more abundant in the exhausted T cells than in the fresh T cells was Sprouty-2, which, other studies had shown, slows down the MAPK/ERK pathway.
Suspecting that Sprouty-2 could be the culprit in T cell exhaustion, Chiu used a specially engineered virus to disable the Sprouty-2 gene in some T cells and found that they were more likely to retain all of their functions than were the cells with working Sprouty-2.
The researchers found that in one experiment, reducing the amount of Sprouty-2 in exhausted HIV-fighting T cells partially restored them. They next tried disabling both Sprouty-2 and PD-1 in the HIV-fighting cells and that reversed the exhaustion completely.