Figure 3.

Complement Independent functions of Complement Regulators. Viral infection begins with the attachment of the virus to the epithelial cell surface via cell surface receptors (1) and the internalisation of the virion through endocytosis and fusion (2). Post endocytosis, viral RNA is released into the cytoplasm (3,4), from where it is transported into the nucleus. In the nucleus, the viral RNA undergoes replication and transcription (5). The transcribed mRNA is translated to viral proteins (6). This is followed by the assembly of the virion and subsequent release of the virion from the cell (7,8,9). C1q, C4BP, Properdin, factor H, and VCP have individually been shown to inhibit the entry of viruses, such as the H1N1 subtype of the Influenza A Virus (IAV), (represented by red virion) into the cell and downregulate inflammatory cytokines and chemokines (TNF-α, IL-6, IL-12, NF-κB, RANTES). However, these complement regulators individually have also been implicated in promoting viral entry, as seen in the case of H3N2 subtype of IAV, and promoting the inflammatory response by upregulating cytokine and chemokines (TNF-α, IL-6, IL-12, NF-κB, and RANTES). These mechanisms of modulating viral entry in a subtype specific manner, occur in the absence of other complement factors and immune cells, suggesting complement independent viral infection modulating activity for these complement regulatory proteins.