Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis

Abstract

The complement system is a critical part of host defense to many bacterial, viral, and fungal infections. It works alongside pattern recognition receptors to stimulate host defense systems in advance of activation of the adaptive immune response. In this study, we directly test the role of complement in SARS-CoV pathogenesis using a mouse model and show that respiratory disease is significantly reduced in the absence of complement even though viral load is unchanged. Complement-deficient mice have reduced neutrophilia in their lungs and reduced systemic inflammation, consistent with the observation that SARS-CoV pathogenesis is an immune-driven disease. These data suggest that inhibition of complement signaling might be an effective treatment option following coronavirus infection.

IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes

“…In complete contrast to the early IFN treatment results, delayed IFN treatment resulted in a robust proinflammatory response and did not improve virus clearance (Figure 6, D-I). Notably, we detected upregulation of genes involved in coagulation molecules, which were shown to contribute to severe disease in SARS-CoV-infected mice (63). Ineffective control of virus replication is likely due to IFN and ISG antagonism by viral proteins, and/or the result of impaired virus-specific T cell responses (14,64).…”

Increasing Host Cellular Receptor—Angiotensin-Converting Enzyme 2 (ACE2) Expression by Coronavirus may Facilitate 2019-nCoV Infection

“…We retried microarray database submitted in NCBI and analysis ACE2 expression levels during virus infection. In lungs from C57Bl/6 mouse infected with 10 2 PFU SARS-CoV, ACE2 mRNA is significantly increased comparing with the mock group 1 6 / 2 2 ( Figure 4) (Gralinski et al, 2018;Totura et al, 2015). In primary human airway epithelial cells, MERS-CoV infection can obviously increase ACE mRNA levels at 24, 36 and 48 hours post infection ( Figure 5).…”

Coronavirus infections and immune responses

“…C3a and C5a blockade acts as a treatment for acute lung injury, and anti‐C5a antibody shows to protect mice from infection with MERS‐CoV 91 . SARA‐CoV infection activates the complement pathway and complement signaling contributes to disease 92 …”