Complement Decay-Accelerating Factor is a modulator of influenza A virus lung immunopathology
DownLoad
Clearance of viral infections, such as SARS-CoV-2 and influenza A virus (IAV), must be
fine-tuned to eliminate the pathogen without causing immunopathology. As such, an aggressive
initial innate immune response favors the host in contrast to a detrimental prolonged
inflammation. The complement pathway bridges innate and adaptive immune system and contributes
to the response by directly clearing pathogens or infected cells, as well as recruiting
proinflammatory immune cells and regulating inflammation. However, the impact of modulating
complement activation in viral infections is still unclear. In this work, we targeted the
complement decay-accelerating factor (DAF/CD55), a surface protein that protects cells from
non-specific complement attack, and analyzed its role in IAV infections. We found that DAF
modulates IAV infection in vivo, via an interplay with the antigenic viral proteins
hemagglutinin (HA) and neuraminidase (NA), in a strain specific manner. Our results reveal that,
contrary to what could be expected, DAF potentiates complement activation, increasing the
recruitment of neutrophils, monocytes and T cells. We also show that viral NA acts on the
heavily sialylated DAF and propose that the NA-dependent DAF removal of sialic acids exacerbates
complement activation, leading to lung immunopathology. Remarkably, this mechanism has no impact
on viral loads, but rather on the host resilience to infection, and may have direct implications
in zoonotic influenza transmissions.
Reference
Santos, N. B., da Silva, Z. E. V., Gomes, C., Reis, C. A., & Amorim, M. J. (2021). Complement Decay-Accelerating Factor is a modulator of influenza A virus lung immunopathology. bioRxiv.
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