Antiviral Role of Toll-Like Receptor-3 Agonists against Seasonal and Avian Influenza Viruses


  1. Wong, J.P.
  2. Christopher, M.E.
  3. Viswanathan, S.
  4. Dai, X.
  5. Salazar, A.M.
  6. Sun, L-Q.
  7. Wang, M.
Corporate Authors
Defence R&D Canada - Suffield, Ralston ALTA (CAN);Oncovir Inc, Washington DC (US);College of Veterinary Medicine China Agriculture University, Beijing (CHINA)
The divergence and antigenic shifts in influenza viruses represent significant challenges for the development of effective vaccines and antiviral drugs against influenza viruses. In view of current challenges and/or deficiencies in the influenza pandemic influenza preparedness, novel antiviral strategies which are robust and can respond to constant viral mutations, are particularly needed to combat future pandemic threats. Toll-like receptor-3 (TLR-3) is an integral part of the host's innate immune system and serves as an important signaling pathway for the recognition of dsRNA for the triggering of antiviral and inflammatory responses to combat viral infections. This review examines dsRNA including Poly ICLC and liposome-encapsulated Poly ICLC (LE Poly ICLC) as TLR-3 agonists for their antiviral activity against seasonal and highly pathogenic avian influenza (HPAI) viruses. Furthermore, their roles in attenuating the antiviral and inflammatory cytokines in the host will also be explored. Preclinical studies in experimental animals suggest Poly ICLC and liposome-encapsulated Poly ICLC are safe and offer broad-spectrum protection against both seasonal and HPAI viruses, as well as other respiratory viruses including respiratory syncytial virus and SARS. Preliminary results from recent studies suggest these drugs up-regulate the production of inter-ferons (-α, -β, and -γ), and tumor necrosis factor (TNF-α) but downregulate some proinflammatory cytokines in
Date of publication
03 May 2010
Number of Pages
Reprinted from
Current Pharmaceutical Design, vol 15, 2009, p 1269-1274
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