The effect of statins on the replication and innate immune response induced by influenza virus.
Session ? – Brookes, Daniel – Poster Only
Title of Contribution: The effect of statins on the replication and innate immune response induced by influenza virus.
Author(s): Daniel Brookes and Wendy Barclay
Affiliation(s): Imperial College London
Abstract: Currently circulating avian influenza H5N1 represents a serious pandemic threat. In such an event, it is unlikely that supplies of both vaccines and stockpiled anti-viral drugs would be sufficient to meet public demand for treatment and prophylaxis, particularly in the developing world. This, coupled with emerging viral resistance against licensed anti-influenza drugs, presents an overwhelming demand for other effective therapeutics to use against influenza. In view of the enhanced induction of cytokines by both the 1918 ‘Spanish Influenza’ H1N1 and currently circulating H5N1 virus strains (de Jong, et al., 2006), it has been suggested that immunomodulatory and anti-inflammatory agents may be beneficial should a pandemic strain of this phenotype emerge. Statins exhibit pleiotropic effects and are known to inhibit the formation of pro-inflammatory cytokines and chemokines induced by influenza infection (Terblanche, et al., 2007). The worldwide availability and low production cost make statins an attractive therapeutic option. Moreover epidemiological data support a benefit of statin use against influenza-related pneumonia. Therefore we have assessed the immunomodulatory effect of statins on the host innate immune response induced during influenza infection. Furthermore, influenza haemagglutinin and neuraminidase proteins are reliant on cholesterol inside the cell for efficient translocation to the cell surface (Keller and Simons, 1998). We also assessed whether the cholesterol-lowering properties of statins contribute to a direct antiviral effect that would boost the credentials of statins as an alternative to established influenza treatments.
de Jong M. D., Simmons, C. P., Thanh, T. T., et al. (2006) Fatal outcome of human
infl uenza A (H5N1) is associated with high viral load and hypercytokinemia. Nature Medicine 12: 1203–07.
Keller, P. & Simons, K. (1998) Cholesterol is required for surface transport of influenza virus hemagglutinin. Journal of Cell Biology 140, 1357-1367.
Terblanche, M., Almog, Y., Rosenson, R. S., Smith, T. S. & Hackam, D. G. (2007), Statins and sepsis: multiple modifications at multiple levels. Lancet Infectious Diseases 7, 355-68.
