Influenza Virus Infection is not Affected by Serum Amyloid P Component

Jeff Herbert,Ken-Ichi Yamamura,Roland Jakob-Roetne,Jane Ives,Misao Suzuki,Winston L Hutchinson,Jackie Carr,Mark B Pepys

doi:10.1007/bf03401998

Abstract

Binding of serum amyloid P component (SAP) to its ligands, including bacteria, chromatin and amyloid fibrils, protects them from degradation, is anti-opsonic and anti-immunogenic. SAP thereby enhances the virulence of pathogenic bacteria to which it binds. However SAP also contributes to host resistance against bacteria to which it does not bind. Human SAP has been reported to bind to the influenza virus and inhibit viral invasion of cells in tissue culture. We therefore investigated a possible role of SAP in either host resistance or viral virulence during influenza infection in vivo. The clinical course of mouse adapted influenza virus infection, the host antibody response, and viral replication, were compared in wild type mice, mice with targeted deletion of the SAP gene, and mice transgenic for human SAP. The effects of reconstitution of SAP deficient mice with pure human SAP, and of a drug that specifically blocks SAP binding in vivo, were also studied. Binding of mouse and human SAP to immobilized influenza virus was compared. The presence, absence, or availability for binding of SAP in vivo had no significant or consistent effect on the course or outcome of influenza infection, or on either viral replication or the anti-viral antibody response. Mouse SAP bound much less avidly than human SAP to influenza virus. In marked contrast to the dramatic effects of SAP deficiency on host resistance to different bacterial infections, mouse SAP apparently plays no significant role during infection of mice with influenza virus. Human SAP binds much more avidly than mouse SAP to the virus, but also had no effect on any of the parameters measured and is therefore unlikely to be involved in human influenza infection.

Highlights

Serum amyloid P component (SAP), a normal plasma protein of the pentraxin family [1], binds to amyloid fibrils, to certain anionic glycans, to DNA, chromatin and apoptotic cells, and to some bacteria [2]
We have investigated the clinical course and immune response to mouse adapted strains of influenza virus in serum amyloid P component (SAP) deficient compared to wild type mice, as Molecular Medicine, Volume 8, Number 1, January 2002 well as in human SAP transgenic animals, and mice treated with our novel SAP-inhibitory drug [7]
There was no consistent difference between normal wild type mice and SAP knockout mice, regardless of the severity of infection, with respect to the clinical course or outcome (Figs. 1 and 2), virus shedding in nasal washes (Table 1), virus titers in the lung (Table 2), or anti-viral antibody titers in the blood or bronchoalveolar lavage fluid (Table 2)

Summary

Introduction

Serum amyloid P component (SAP), a normal plasma protein of the pentraxin family [1], binds to amyloid fibrils, to certain anionic glycans, to DNA, chromatin and apoptotic cells, and to some bacteria [2]. SAP bound to all these ligands acts as an anti-opsonin, protecting them from degradation in vitro and in vivo [3,4] This contributes to pathogenesis of amyloidosis [5]. Human SAP binds to the influenza virus hemagglutinin and inhibits invasion of cells in vitro, whilst preincubation of the virus with human SAP in vitro or intra-nasal administration of human SAP to mice, have been reported to prevent infection in vivo [8,9]. These observations suggest that SAP might play a role in innate immunity to influenza infection. We have investigated the clinical course and immune response to mouse adapted strains of influenza virus in SAP deficient compared to wild type mice, as Molecular Medicine, Volume 8, Number 1, January 2002 well as in human SAP transgenic animals, and mice treated with our novel SAP-inhibitory drug [7]

Materials and Methods

Results

Discussion