Understanding the Role of the Complement System in Ebola Virus and SARS-CoV-2 Pathogenesis

Jack Mellors
The role of the complement system in viral infections is often complex, with significant implications for pathogenesis and disease. The complement system can form part of the early innate immune response through the binding of glycosylated viral proteins, or through spontaneous activation on viral surfaces. The complement system can also be activated by antibodies in complex with viral antigens. These mechanisms have the potential to inhibit virus interactions with host proteins, mediate
more » ... ation, promote inflammation and chemotaxis, cause the agglutination of virions, lyse virions, and lyse virus-infected cells. Despite the diverse and significant roles of the complement system in viral infection, it is a relatively under-researched aspect of antiviral immunity. The complement system has been associated with more severe symptoms and fatal outcomes of Ebola virus (EBOV) disease (EVD) and Coronavirus disease (COVID)-19. However, the underlying mechanisms of the complement system in response to EBOV and SARS-CoV-2 (the causative agent of COVID-19), and the wider implications for immunity, are poorly understood. We first investigated the antibody-independent mechanisms of the complement system in response to Ebolavirus and Coronavirus glycoproteins (GPs), to better understand the underlying mechanisms of complement activation in the early stages of infection. Using novel ELISAs and western blot assays, we identified MBL binding to a range of Ebolavirus and Coronavirus GPs, and demonstrated their potential to activate the complement system, eventuating in formation of the membrane attack complex (MAC). We also utilised PCR assays, next-generation sequencing, and LC-MS/MS, to identify potential differences in the structure and expression of complement proteins in EVD survivors. We found broad diversity in the SNPs of several complement proteins but were restricted by the sample size to determine significance. These findings showed potential mechanisms for antibody-independent complement activation that could influ [...]
doi:10.17638/03159925 fatcat:z36etkhx2rdffdggnpxjq4za7e