Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/20285
Title: Complement-independent Modulation of Influenza A virus infection by Factor H
Authors: Murugaiah, V
Varghese, P
Saleh, S
Tsolaki, A
Alrokayan, S
Khan, H
Collison, K
Sim, R
Nal, B
Al-Mohanna, F
Kishore, U
Keywords: Innate immunity;Complement;Factor H;Vaccinia virus complement control protein;Influenza A virus;Pseudotyped lentiviral particles;Cytokines storm
Issue Date: 2020
Publisher: Frontiers Media
Citation: Frontiers in Immunology
Abstract: The complement system is an ancient innate immune defence mechanism that can recognise molecular patterns on the invading pathogens. Factor H, as an inhibitor of the alternative pathway, down-regulates complement activation on the host cell surface. Locally synthesised factor H at the site of infection/injury, including lungs, can act as a pattern recognition molecule without involving complement activation. Here, we report that factor H, a sialic acid binder, interacts with influenza A virus (IAV) and modulates IAV replication, as observed by an upregulation of matrix protein 1 (M1) expression in H3N2-infected A549 cells, while downregulating M1 in H1N1 subtype-infected cells. Far-western blot revealed that factor H binds hemagglutinin (HA, ~70kDa), neuraminidase (NA, ~60kDa), and M1 (~25kDa). IAV-induced transcriptional levels of IFN-α, TNF-α, IL-12, IL-6, IFN-α, while RANTES were reduced following factor H treatment for the H1N1 subtype at 6 h post-infection. However, for the H3N2 subtype, mRNA levels of these pro-inflammatory cytokines were enhanced. Recombinant form of vaccinia virus complement control protein (VCP), which like factor H, contains CCP modules and has complement-regulatory activity, mirrored the results obtained with factor H. Both factor H (25%) and VCP (45%) were found to reduce luciferase reporter activity in MDCK cells transduced with H1N1 pseudotyped lentiviral particles. Factor H (50%) and VCP (30%) enhanced the luciferase reporter activity for H3N2, suggesting an entry inhibitory role of factor H and VCP against H1N1, but not H3N2. Thus, factor H can modulate IAV infection and inflammatory response independent of its complement-related functions.
URI: http://bura.brunel.ac.uk/handle/2438/20285
DOI: http://dx.doi.org/10.3389/fimmu.2020.00355
ISSN: 1664-3224
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