Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies

Serum amyloid P component (SAP) binds in vitro Ca2+-dependently to several ligands including oligosaccharides with terminal mannose and galactose. We have earlier reported that SAP binds to human influenza A virus strains. in hibiting hemagglutinin (HA) activity and virus infectivity in vitro. These studies were extended to comprise five mouse-adapted influenza A strains. t wo swine influenza A strains, a mink influenza A virus. a ferret influenza A reassortant virus, a influenza B virus and a parainfluenza 3 virus. The H A activity of all these viruses was inhibited by SAP. Western blotting show ed that SAP bound to HA trimers, monomers and HA1 and HA2 subunits of influ enza A virus. Binding studies indicated that galactose, mannose and fucose moieties contributed to the SAP reacting site(s). Intranasal administration of human SAP to mice induced no demonstrable toxic reactions, and circulat ing antibodies against SAP were not detected. Preincubation of virus (A/Jap an/57) with SAP prevented primary infection of mice and development of anti viral antibodies. After a single intranasal administration of SAP (40 mug) 1 h before primary infection with virus (2LD(50)), nine out of 10 mice surv ived on day 10 and these mice approached normal body weight, whereas contro l mice (one out of five surviving on day 10) died. The data provide evidenc e of the potential of intranasally administered SAP for prophylactic treatm ent of influenza A virus infections in humans. (C) 2001 Elsevier Science B. V. All rights reserved.