New research from a collaboration between the University of Bonn, University of Cologne, and the Technical University of Munich has led to the discovery of an explanation for why certain viral infections are chronic and others are not. This same discovery has promise for generating new therapeutic targets.
Helper T cells secrete inflammatory messengers, a kind of “distress call” to killer T cells to come to their aid and fight off invading pathogens. However, viruses that cause a chronic infection, like HIV, employ virulence factors to silence these messages, ironically rendering the helper T cells helpless and ineffective.
In the recent collaborative study, published in the journal Nature Immunology, scientists studied mice models of chronic viral infection to see which helper T cell genes remain active when silenced by viruses. They were able to implicate tumor necrosis factor (TNF) as an agent of chronic viral infection. TNF controls various signaling pathways that inhibit helper T cell activity during chronic inflammation. In mice suffering from HIV-esque chronic viral infections with TNF inactivated, helper T cells produce inflammatory messengers like normal.
“After ten days, the animals had completely eliminated the virus; they were healthy,” explained Dr. Marc Beyer from the University of Bonn.
Meanwhile, during acute viral infections, TNF has the opposite effect. It boosts the immune system and stimulates apoptosis in cells corrupted by viral particles.
“In an acute infection, large quantities of TNF are formed very rapidly," said Dr. Zeinab Abdullah from the University of Bonn. "In chronic infections, on the other hand, the body secretes small amounts of TNF over a long period of time. This appears to cause the helper T cells to shut down to some extent."
The difference seems to stem from some sort of protective mechanism that prevents healthy tissues from being damaged from persistent inflammation, however the team is still in the dark about how exactly TNF works on a molecular level. For the time being, TNF inhibitors could be useful as a therapeutic treatment for patients with chronic viral infections like they are currently used for patients with rheumatoid arthritis and other autoimmune diseases.
Source: University of Bonn