Flagellin

Flagellin Fragments as Potential Treatment for Chronic Viral Infections

Application

The use of flagellin and its fragments for treating chronic viral infections (CVI) including infections caused by HIV, Hepatitis viruses, Rotaviruses and Cytomegalovirus.

Key Benefits

Administration of Toll-like receptor-5 (TLR5) agonist - flagellin resolves a chronic rotaviral infection in mice.
Flagellin protects mice from rotavirus infection in a dose-dependent manner.
May present fewer side-effects than pre-existing viral therapies.

Technical Summary

Dr. Gewirtz's group at Emory has demonstrated the surprising finding that flagellin, an essential component of bacterial flagellum, can resolve a chronic rotavirus infection in immunodeficient mice. This effect was mediated through TLR5 that activates the host's innate immune system. Unlike TLR3, 7 and 9, TLR-5 was previously not thought to play a role in mitigating preexisting viral infections as it does not recognize viral components. Thus, the use of flagellin as an antidote for CVI is a novel paradigm in antiviral therapy.

Traditional therapeutics to treat viral infections includes inhibitors for enzymes which cripple viral functions or interferon therapies which enhance viral presentation to host immune cells. These therapies have a high failure rate due to drug resistance that develops over long-term use as well as toxic side-effects. On the other hand, TLR-based therapeutics work by activating the host immune system and are known to present milder side-effects. Moreover, flagellin therapy may work in conjunction with other preexisting or failed antiviral therapies.

Developmental Stage

In-vivo proof of principle has been demonstrated in a rodent model.
Further studies testing the therapeutic properties of flagellin in chronic infection models for influenza and LCMV are underway.