The complement system plays a dual role in viral infections and in therapeutic utilization of viral vectors. The complement as part of the innate immunity of the antiviral immune response limits infection by preventing attachment of viruses to viral receptors. Opsonization by C3b and or C4b proteolytic fragments may induce aggregation, lysis and clearance by phagocytic cells (Blue CE, Spiller OB 2004 Virology). This could inhibit therapeutic efficacy of viral vectors (Zaiss AK, Cotter MJ 2008 J Virol; Hotte SJ, Lorence RM 2007 Clin Cancer Res) and complement depletion may facilitate infection of tumor cells targeted by therapeutic viral vectors (Ikeda K, Wakimoto H 2000 J Virol). Virion N-glycans may serve as complement binding sites (Fraser IP, Koziel H 1998 Semin Immunol; Hubbard SC 1988 JBC; Ji X, Olinger GG 2005 J Gen Virol). Therefore, modulation of complement binding by modification of virion N-Glycan structures may be used to regulate elimination of virions by the complement system (Morizono K, Ku A 2010 J Virol). Also, incorporation of host complement regulatory proteins into virions may enhance complement evasion (Biswas M, Johnson JB 2012 J Virol).
In addition, virus induced complement activation may lead to inflammation, tissue injury (Zhang Z, Li Y 2010 Virol J) and / or acute respiratory distress (Hartman ZC, Appledorn DM 2008 Virol). Engineering viruses to reduce complement activation or application of complement inhibitors (Ricklin D, Lambris JD 2013 J Immunol) can therefore limit undesired side effects of viral therapy.
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