Scientists at Duke University Medical School and Mount Sinai School of Medicine have discovered a new role for a host protein that provides further insight into how CD8+ T cells work to control HIV and other infections. The finding could yield new strategies for prevention or treatment.
The discovery centres around the anti-HIV function of a tiny protein called prothymosin-alpha.
Previous studies have shown that the protein can block HIV viral replication once HIV invades a cell, but until now, no one has understood exactly how that happened.
"But now we have a much clearer understanding of how this protein works," said Dr. Mary Klotman, senior author of the paper.
The discovery of the antiviral activity of this protein is another piece of the long-standing quest to define the natural substances made by specific immune cells, in this case CD8+ T cells, that have potent anti-HIV activity.he researchers conducted a series of laboratory tests and studies in mice and in human cells, and discovered that prothymosin-alpha binds to an important cell receptor called TLR4, and stimulates these cells to produce interferon.
Interferons are part of the body's innate immune system and are powerful, naturally occurring proteins that can kill many types of pathogens, including bacteria, cancer cells and viruses, like HCV and HIV.
"We found this fascinating. Usually, it takes an invading virus to trigger interferon production. But here we have a case where the body's own defense system - a host protein - is inducing it," said Klotman.
"This is a perfect example of two arms of the immune system working together. A protein produced by CD8+ cells of the adaptive immune system is exerting potent viral-suppressive activity through a mechanism thought to be reserved for cells of the innate immune system," said a co-author of the study.
The researchers performed their experiments in macrophages, special immune cells that are one of the first lines of defense against viruses and infectious microbes, and also among the key targets HIV invades.
"Macrophages are also important because we think they also function as a safe haven for HIV; protective spaces where HIV can hide and bide its time. It's good to know we've identified a pathway that we might be able to exploit to sabotage this function," said Klotman.
The scientists said that figuring out how prothymosin-alpha stimulates production of interferon could reveal novel pathways for protection and treatment of viral infections.
"But much more work needs to be done. The structure of the protein invites interaction with other proteins that could potentially affect its current function," they said.
The study has been published in the Proceedings of the National Academy of Sciences.