Human C1q Regulates Influenza A Virus Infection and Inflammatory Response via Its Globular Domain.

Praveen M Varghese,Reena Rajkumari,Uday Kishore

doi:10.3390/ijms23063045

Abstract

The Influenza A virus (IAV) is a severe respiratory pathogen. C1q is the first subcomponent of the complement system’s classical pathway. C1q is composed of 18 polypeptide chains. Each of these chains contains a collagen-like region located at the N terminus, and a C-terminal globular head region organized as a heterotrimeric structure (ghA, ghB and ghC). This study was aimed at investigating the complement activation-independent modulation by C1q and its individual recombinant globular heads against IAV infection. The interaction of C1q and its recombinant globular heads with IAV and its purified glycoproteins was examined using direct ELISA and far-Western blotting analysis. The effect of the complement proteins on IAV replication kinetics and immune modulation was assessed by qPCR. The IAV entry inhibitory properties of C1q and its recombinant globular heads were confirmed using cell binding and luciferase reporter assays. C1q bound IAV virions via HA, NA and M1 IAV proteins, and suppressed replication in H1N1, while promoting replication in H3N2-infected A549 cells. C1q treatment further triggered an anti-inflammatory response in H1N1 and pro-inflammatory response in H3N2-infected cells as evident from differential expression of TNF-α, NF-κB, IFN-α, IFN-β, IL-6, IL-12 and RANTES. Furthermore, C1q treatment was found to reduce luciferase reporter activity of MDCK cells transfected with H1N1 pseudotyped lentiviral particles, indicative of an entry inhibitory role of C1q against infectivity of IAV. These data appear to demonstrate the complement-independent subtype specific modulation of IAV infection by locally produced C1q.

Highlights

Influenza viruses are negativestrand RNA viruses belonging to the Orthomyxoviridae family. They are classified into four genera: influenza A virus (IAV), influenza B virus (IBV), influenza C virus (ICV), and influenza D virus (IDC)
Far-Western blotting was performed in order to determine the IAV proteins that interacted with human C1q (Figure 2)
After treatment of H1N1 particles with factor H, Vaccinia virus complement control protein (VCP), or C4BP, A549 cells showed a decrease in M1 expression

Summary

Introduction

Known as the flu, is an acute viral infection that affects the upper or lower respiratory tract. Influenza viruses are negativestrand RNA viruses belonging to the Orthomyxoviridae family. They are classified into four genera: influenza A virus (IAV), influenza B virus (IBV), influenza C virus (ICV), and influenza D virus (IDC). Only the IAV has been attributed to causing pandemics that can have devastating consequences if not treated or prevented. They occur approximately three times every century when viral antigens present in avian circulating strains are acquired by human influenza strains [4]

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